<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03301740</url>
  </required_header>
  <id_info>
    <org_study_id>17-1057</org_study_id>
    <secondary_id>1K23DK109401</secondary_id>
    <nct_id>NCT03301740</nct_id>
  </id_info>
  <brief_title>Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis</brief_title>
  <official_title>Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The rate of fluid removal (ultrafiltration, UF) during hemodialysis (HD) may contribute to&#xD;
      cardiovascular morbidity and mortality among individuals receiving maintenance HD. More rapid&#xD;
      UF rates are associated with higher morbidity and mortality. Ultrafiltration profiling, the&#xD;
      practice of varying UF rates to maximize fluid removal during periods of greatest hydration&#xD;
      and plasma oncotic pressures, is one treatment modification that may reduce UF-related harm&#xD;
      without necessitating reduction in interdialytic fluid intake or longer HD treatments. To&#xD;
      date, UF profiling has not been adequately studied independent of sodium profiling.&#xD;
&#xD;
      This study investigates the comparative effect of UF profiling versus non-profiled&#xD;
      conventional HD on select cardiovascular and patient-reported outcomes. Participants will&#xD;
      complete two phases of UF profiling and two phases of conventional HD and will act as their&#xD;
      own controls.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 12, 2018</start_date>
  <completion_date type="Actual">December 18, 2018</completion_date>
  <primary_completion_date type="Actual">December 15, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The study is a 4-phase crossover trial in which participants are successively alternated between conventional HD and conventional HD + linear UF profiling across 4 phases with intervening wash-out periods. The study compares conventional HD (the participant's standard HD prescription with no UF profiling) to conventional HD + linear UF profiling. Participants will be randomly allocated to conventional HD or conventional HD + linear UF profiling for phase 1. Participants will undergo 9 treatments during each phase for a total of 18 conventional HD treatments and 18 UF profiled treatments. Participants will undergo 3 wash-out HD treatments between phases.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The study will be double-blinded in that participants will not be informed of the treatment paradigm. Investigators, including those performing transthoracic echocardiography (TTE) interpretation, will be blinded to treatment paradigm. Ultrasonographers performing intra-HD TTEs will be blinded to treatment paradigm.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP &lt;90 mmHg)</measure>
    <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
    <description>Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP &lt;90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis</measure>
    <time_frame>Weeks 3, 7, 11, and 15</time_frame>
    <description>Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment</measure>
    <time_frame>Weeks 3, 7, 11, and 15</time_frame>
    <description>Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change ≥10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)</measure>
    <time_frame>Weeks 3 and 7</time_frame>
    <description>Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nadir Systolic Blood Pressure During Hemodialysis in mmHg</measure>
    <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
    <description>Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is &gt;1 kg or &lt;-1 kg)</measure>
    <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
    <description>The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was &gt;1 kg or &lt;-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)</measure>
    <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
    <description>Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>UF Profiling Phase First</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First treatment phase begins with linear UF profiling during HD.&#xD;
Participants randomized to starting with the experimental UF profiling phase will receive 9 HD treatments with UF profiling (1st experimental phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 conventional HD treatments (1st control phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional HD Phase First</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First treatment phase begins with conventional HD.&#xD;
Participants randomized to starting with the control conventional HD phase will receive 9 conventional HD treatments (1st control phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 HD treatments with UF profiling (1st experimental phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>UF profiling during HD</intervention_name>
    <description>Experimental arm: Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; pre-programmed &quot;profile 2&quot; on a Fresenius 2008K machine, the machine used in all participating clinics). Ultrafiltration profiling will be performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
    <arm_group_label>Conventional HD Phase First</arm_group_label>
    <arm_group_label>UF Profiling Phase First</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional HD</intervention_name>
    <description>Control arm: Conventional HD (routine care) is the participant's standard HD prescription without UF profiling.</description>
    <arm_group_label>Conventional HD Phase First</arm_group_label>
    <arm_group_label>UF Profiling Phase First</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  UF rate &gt;10 mL/h/kg in &gt;30% of treatments in a 30-day screening period (require ≥6&#xD;
             outpatient HD treatments in this period)&#xD;
&#xD;
          -  Age 18-85 years&#xD;
&#xD;
          -  Ability to converse comfortably in English or Spanish&#xD;
&#xD;
          -  Receipt of in-center maintenance HD at Carolina Dialysis clinics in Carrboro or Siler&#xD;
             City, North Carolina&#xD;
&#xD;
          -  ≥90 days on HD&#xD;
&#xD;
          -  Free of bloodstream infection during screening period&#xD;
&#xD;
          -  Willingness to undergo all study testing&#xD;
&#xD;
          -  Evidence of a signed and dated informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Systolic BP unable to be measured by arm cuff&#xD;
&#xD;
          -  &gt;1 hospitalization during screening period&#xD;
&#xD;
          -  Unstable angina per treating nephrologist&#xD;
&#xD;
          -  End-stage cirrhosis per treating nephrologist&#xD;
&#xD;
          -  New York Heart Association class IV heart failure per treating nephrologist&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  More than 4 times per week HD&#xD;
&#xD;
          -  Incarcerated&#xD;
&#xD;
          -  Anticipated kidney transplant within 6 months per treating nephrologist&#xD;
&#xD;
          -  Non-adherence to HD prescription (&gt;2 unexplained absences during screening period)&#xD;
&#xD;
          -  Sodium profiling or UF profiling in standard HD prescription&#xD;
&#xD;
          -  Decisionally challenged, unable to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer Flythe, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolina Dialysis - Carrboro</name>
      <address>
        <city>Carrboro</city>
        <state>North Carolina</state>
        <zip>27510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Dialysis - Siler City</name>
      <address>
        <city>Siler City</city>
        <state>North Carolina</state>
        <zip>27344</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <results_first_submitted>November 20, 2019</results_first_submitted>
  <results_first_submitted_qc>May 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 15, 2020</results_first_posted>
  <last_update_submitted>May 14, 2020</last_update_submitted>
  <last_update_submitted_qc>May 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ultrafiltration profiling</keyword>
  <keyword>Hemodialysis</keyword>
  <keyword>Dialysis</keyword>
  <keyword>Cardiovascular outcomes</keyword>
  <keyword>Patient-reported outcomes</keyword>
  <keyword>Crossover study design</keyword>
  <keyword>End Stage Renal Disease</keyword>
  <keyword>Ultrafiltration</keyword>
  <keyword>Echocardiogram</keyword>
  <keyword>Blood pressure</keyword>
  <keyword>Hypotension</keyword>
  <keyword>Symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 4, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT03301740/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>UF Profiling Phase First</title>
          <description>First treatment phase begins with linear UF profiling during HD.&#xD;
Participants randomized to starting with the experimental UF profiling phase will receive 9 HD treatments with UF profiling (1st experimental phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 conventional HD treatments (1st control phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase).</description>
        </group>
        <group group_id="P2">
          <title>Conventional HD Phase First</title>
          <description>First treatment phase begins with conventional HD.&#xD;
Participants randomized to starting with the control conventional HD phase will receive 9 conventional HD treatments (1st control phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 HD treatments with UF profiling (1st experimental phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1 Intervention (3 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>First Washout (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Phase 2 Intervention (3 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Kidney Transplant</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Washout (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Phase 3 Intervention (3 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Third Washout (1 Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Phase 4 Intervention (3 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Prolonged Hospitalization</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>UF Profiling Phase First</title>
          <description>First treatment phase begins with linear UF profiling during HD.&#xD;
Participants randomized to starting with the experimental UF profiling phase will receive 9 HD treatments with UF profiling (1st experimental phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 conventional HD treatments (1st control phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase).</description>
        </group>
        <group group_id="B2">
          <title>Conventional HD Phase First</title>
          <description>First treatment phase begins with conventional HD.&#xD;
Participants randomized to starting with the control conventional HD phase will receive 9 conventional HD treatments (1st control phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 HD treatments with UF profiling (1st experimental phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55" spread="15"/>
                    <measurement group_id="B2" value="57" spread="15"/>
                    <measurement group_id="B3" value="56" spread="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP &lt;90 mmHg)</title>
        <description>Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP &lt;90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP &lt;90 mmHg)</title>
          <description>Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP &lt;90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="578"/>
                    <measurement group_id="O2" value="571"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in intradialytic hypotension between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.5</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>1.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis</title>
        <description>Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).</description>
        <time_frame>Weeks 3, 7, 11, and 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis</title>
          <description>Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" lower_limit="4.4" upper_limit="20.2"/>
                    <measurement group_id="O2" value="11.3" lower_limit="3.4" upper_limit="19.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in troponin T change between UF profiling and conventional HD. Repeated measure linear regression was performed, giving each subject a random intercept term. The coefficient is the difference in the outcome between UF profiling and conventional HD.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.2</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Beta coefficient</param_type>
            <param_value>-2.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.9</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment</title>
        <description>Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change ≥10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 3, 7, 11, and 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment</title>
          <description>Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change ≥10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                    <measurement group_id="O2" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in troponin T rise between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.1</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)</title>
        <description>Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.</description>
        <time_frame>Weeks 3 and 7</time_frame>
        <population>All participants who had baseline GLS measurement and had one GLS measurement in each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)</title>
          <description>Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.</description>
          <population>All participants who had baseline GLS measurement and had one GLS measurement in each study arm.</population>
          <units>GLS change (%)</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" lower_limit="-0.1" upper_limit="1.8"/>
                    <measurement group_id="O2" value="1.3" lower_limit="0.1" upper_limit="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in left ventricular GLS change between UF profiling and conventional HD. Wilcoxon (Mann-Whitney) tests were performed assessing the difference of the endpoint between the 2 treatment groups.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.2</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Nadir Systolic Blood Pressure During Hemodialysis in mmHg</title>
        <description>Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).</description>
        <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Nadir Systolic Blood Pressure During Hemodialysis in mmHg</title>
          <description>Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.9" lower_limit="98.4" upper_limit="111.4"/>
                    <measurement group_id="O2" value="102.1" lower_limit="95.5" upper_limit="108.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in nadir systolic BP between UF profiling and conventional HD. Repeated measure linear regression was performed, giving each subject a random intercept term. The coefficient is the difference in the outcome between UF profiling and conventional HD.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.9</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Beta coefficient</param_type>
            <param_value>-0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>1.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is &gt;1 kg or &lt;-1 kg)</title>
        <description>The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was &gt;1 kg or &lt;-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is &gt;1 kg or &lt;-1 kg)</title>
          <description>The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was &gt;1 kg or &lt;-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="578"/>
                    <measurement group_id="O2" value="571"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in failed target weight achievement between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.8</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.7</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)</title>
        <description>Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)</title>
          <description>Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important cramping between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.9</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4</ci_lower_limit>
            <ci_upper_limit>2.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)</title>
        <description>Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)</title>
          <description>Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important nausea/upset stomach between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.5</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2</ci_lower_limit>
            <ci_upper_limit>2.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)</title>
        <description>Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)</title>
          <description>Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important Vomiting/throwing up score between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>1.0</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1</ci_lower_limit>
            <ci_upper_limit>16.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)</title>
        <description>Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)</title>
          <description>Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important dizziness/lightheadedness between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.04</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)</title>
        <description>Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)</title>
          <description>Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important racing heart/heart palpitations between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.3</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3</ci_lower_limit>
            <ci_upper_limit>32.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)</title>
        <description>Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)</title>
          <description>Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important chest pain between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>1.0</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2</ci_lower_limit>
            <ci_upper_limit>6.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)</title>
        <description>Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)</title>
          <description>Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important shortness of breath between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.7</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3</ci_lower_limit>
            <ci_upper_limit>6.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)</title>
        <description>Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)</title>
          <description>Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important thirst/dry mouth between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.2</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3</ci_lower_limit>
            <ci_upper_limit>1.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)</title>
        <description>Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)</title>
          <description>Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important headache between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.8</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4</ci_lower_limit>
            <ci_upper_limit>2.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)</title>
        <description>Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)</title>
          <description>Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important itching between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.02</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.2</ci_lower_limit>
            <ci_upper_limit>6.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)</title>
        <description>Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)</title>
          <description>Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important restless legs/difficulty keeping legs still between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.7</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)</title>
        <description>Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
        <time_frame>Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15</time_frame>
        <population>All participants who completed at least one phase of each study arm.</population>
        <group_list>
          <group group_id="O1">
            <title>UF Profiling</title>
            <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
          </group>
          <group group_id="O2">
            <title>Conventional HD</title>
            <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)</title>
          <description>Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).</description>
          <population>All participants who completed at least one phase of each study arm.</population>
          <units>Number of occurrences</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245"/>
                    <measurement group_id="O2" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = no difference in clinically important tingling/feeling of pins and needles between UF profiling and conventional HD. Likelihood ratio tests were performed using repeated measure logistic regression with the binary treatment indicator as a fixed effect predictor and assigning each subject a random intercept term. A likelihood ratio test assessed the significance of whether the coefficient corresponding to the binary treatment indicator equals to zero.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The equivalence margin is the standard error of the estimated differences between UF and standard treatment from the repeated measure mixed model.</non_inferiority_desc>
            <p_value>0.5</p_value>
            <p_value_desc>Statistically significant p-value is &lt;0.05</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.2</ci_lower_limit>
            <ci_upper_limit>2.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time informed consent is obtained to study participation end, up to 21 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>UF Profiling</title>
          <description>Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; preprogrammed &quot;profile 2&quot; on a Fresenius 2008K machine). Ultrafiltration profiling performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.</description>
        </group>
        <group group_id="E2">
          <title>Conventional HD</title>
          <description>Conventional HD (routine care) is the participant's standard HD prescription without UF profiling</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypervolemia</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Clostridium difficile diarrhea</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone fracture</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="8" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Arteriovenous vascular access surgery</sub_title>
                <description>Missed study treatment due to hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jennifer E. Flythe, MD, MPH</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>(919) 445-2656</phone>
      <email>jflythe@med.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03301740
org study id: 17-1057
secondary id: 1K23DK109401
nct id: NCT03301740
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The rate of fluid removal (ultrafiltration, UF) during hemodialysis (HD) may contribute to
      cardiovascular morbidity and mortality among individuals receiving maintenance HD. More rapid
      UF rates are associated with higher morbidity and mortality. Ultrafiltration profiling, the
      practice of varying UF rates to maximize fluid removal during periods of greatest hydration
      and plasma oncotic pressures, is one treatment modification that may reduce UF-related harm
      without necessitating reduction in interdialytic fluid intake or longer HD treatments. To
      date, UF profiling has not been adequately studied independent of sodium profiling.

      This study investigates the comparative effect of UF profiling versus non-profiled
      conventional HD on select cardiovascular and patient-reported outcomes. Participants will
      complete two phases of UF profiling and two phases of conventional HD and will act as their
      own controls.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study is a 4-phase crossover trial in which participants are successively alternated between conventional HD and conventional HD + linear UF profiling across 4 phases with intervening wash-out periods. The study compares conventional HD (the participant's standard HD prescription with no UF profiling) to conventional HD + linear UF profiling. Participants will be randomly allocated to conventional HD or conventional HD + linear UF profiling for phase 1. Participants will undergo 9 treatments during each phase for a total of 18 conventional HD treatments and 18 UF profiled treatments. Participants will undergo 3 wash-out HD treatments between phases.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The study will be double-blinded in that participants will not be informed of the treatment paradigm. Investigators, including those performing transthoracic echocardiography (TTE) interpretation, will be blinded to treatment paradigm. Ultrasonographers performing intra-HD TTEs will be blinded to treatment paradigm.
measure: Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP <90 mmHg)
time frame: Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
description: Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP <90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis
time frame: Weeks 3, 7, 11, and 15
description: Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).
measure: Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment
time frame: Weeks 3, 7, 11, and 15
description: Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change ≥10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)
time frame: Weeks 3 and 7
description: Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.
measure: Nadir Systolic Blood Pressure During Hemodialysis in mmHg
time frame: Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
description: Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).
measure: Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is >1 kg or <-1 kg)
time frame: Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks
description: The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was >1 kg or <-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
measure: Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)
time frame: Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15
description: Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).
arm group label: UF Profiling Phase First
arm group type: Experimental
description: First treatment phase begins with linear UF profiling during HD.
Participants randomized to starting with the experimental UF profiling phase will receive 9 HD treatments with UF profiling (1st experimental phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 conventional HD treatments (1st control phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase).
arm group label: Conventional HD Phase First
arm group type: Experimental
description: First treatment phase begins with conventional HD.
Participants randomized to starting with the control conventional HD phase will receive 9 conventional HD treatments (1st control phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 HD treatments with UF profiling (1st experimental phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase).
intervention type: Other
intervention name: UF profiling during HD
description: Experimental arm: Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; pre-programmed "profile 2" on a Fresenius 2008K machine, the machine used in all participating clinics). Ultrafiltration profiling will be performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.
arm group label: Conventional HD Phase First
arm group label: UF Profiling Phase First
intervention type: Other
intervention name: Conventional HD
description: Control arm: Conventional HD (routine care) is the participant's standard HD prescription without UF profiling.
arm group label: Conventional HD Phase First
arm group label: UF Profiling Phase First
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jennifer Flythe, MD, MPH
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
sharing ipd: No
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reported events: 
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point of contact: 