<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/NCT03781089</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00088688</org_study_id>
    <nct_id>NCT03781089</nct_id>
  </id_info>
  <brief_title>Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients</brief_title>
  <official_title>Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients Treated With Hemodialysis (PEARL-HD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vifor Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether once-daily dosing of patiromer will reduce&#xD;
      the frequency of hyperkalemic episodes in ESRD (end stage renal disease) study participants&#xD;
      who receive conventional hemodialysis (HD). The study objective is to determine if patiromer&#xD;
      administered orally once a day with breakfast or lunch will reduce episodes of hyperkalemia&#xD;
      in ESRD study participants who receive thrice-weekly HD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice&#xD;
      weekly HD schedule will be screened from retrospective review of clinical and laboratory&#xD;
      parameters from our clinical practice group. A total of 40 study participants (randomized 1:1&#xD;
      study drug: usual care) will be enrolled. Duration of study medication exposure will be 4&#xD;
      weeks. The total duration of study, from enrollment until the end of the washout period will&#xD;
      be 7 weeks.&#xD;
&#xD;
      This is a proof of concept study, to determine whether administration of patiromer has the&#xD;
      potential to change the risk category for ESRD patients who are on conventional HD schedules.&#xD;
      In addition, the study will develop and pilot study procedures that could be implemented in a&#xD;
      large-scale clinical trial. By nature of the limited size of the study, the power of the&#xD;
      trial will be limited. Reducing serum potassium with the use of low dialysate potassium is&#xD;
      actually associated with an increased risk of sudden cardiac death. Furthermore, HD patients&#xD;
      already carry a high pill burden, and it is unclear if prescription of an additional oral&#xD;
      medication will reduce the frequency of episodic hyperkalemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2019</start_date>
  <completion_date type="Actual">March 15, 2023</completion_date>
  <primary_completion_date type="Actual">March 15, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice weekly HD schedule will be screened from retrospective review of clinical and laboratory parameters from our clinical practice group. A total of 40 patients (randomized 1:1 study drug: usual care) will be enrolled. Duration of study medication exposure will be 4 weeks. The total duration of study, from enrollment until the end of the washout period will be 7 weeks.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The study is open-label and therefore the subjects, coordinators and investigators are not blinded to the intervention. Titration of the patiromer will require viewing of the serum potassium values. During the data analysis, however, personnel involved will remain blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of episodes of serum K ≥ 5.5 mEq/L</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine if patiromer administered orally once a day with the mid-day meal will reduce episodes of hyperkalemia in ESRD patients who receive thrice-weekly HemoDiaylsis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of patients with serum K &gt; 5.5 mEq/L</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the between-group differences in percent of patients with serum K &gt; 5.5 mEq/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average dose of patiromer that was given in treatment arm</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the efficacy and dosing of patiromer in ESRD patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of additional hemodialysis treatments due to hyperkalemia.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of significant arrhythmia events as detected with cardiac monitors in Week 4.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the between-group differences in pre-specified significant arrhythmia events as detected with cardiac monitors in Week 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference percentage in serum albumin concentrations.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the between-group differences in serum albumin concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference percentage in PTH concentrations.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine the between-group differences in PTH concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients who completed all study visits.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To determine feasibility of a large-scale hemodialysis-based trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change percentage in serum potassium concentration two weeks after study drug is discontinued.</measure>
    <time_frame>6 weeks</time_frame>
    <description>To determine the change in serum potassium concentration two weeks after study drug is discontinued</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change percentage in serum phosphorus concentration two weeks after study drug has been discontinued.</measure>
    <time_frame>6 weeks</time_frame>
    <description>To determine the change in serum phosphorus concentration two weeks after study drug has been discontinued</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of &gt; 1000 PVC/24 hours.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Presence of &gt; 1000 PVC/24 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of significant arrhythmias.</measure>
    <time_frame>4 weeks</time_frame>
    <description>The between-group and Week-0-to-Week-4-differences in significant arrhythmias will be evaluated.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Hyperkalemia</condition>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>Patiromer Oral Powder Product</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K &lt; 4.0 mEq/L, and patiromer will be discontinued if K &lt; 3.5 mEq/L.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Patiromer Oral Powder Product</intervention_name>
    <description>Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K &lt; 4.0 mEq/L, and patiromer will be discontinued if K &lt; 3.5 mEq/L. Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol</description>
    <arm_group_label>Patiromer Oral Powder Product</arm_group_label>
    <other_name>Valtressa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and Females, age at least 18 years&#xD;
&#xD;
          -  ESRD treated with thrice-weekly HD for ≥ 6 months.&#xD;
&#xD;
          -  At least two measured pre-dialysis serum [K] ≥ 5.5 mEq/L or one [K] ≥ 6.0 mEq/L noted&#xD;
             over the past three months&#xD;
&#xD;
          -  Current use of dialysate with potassium concentration ≤ 2 mEq/L&#xD;
&#xD;
          -  Typical consumption of at least two meals per day&#xD;
&#xD;
          -  Have received customary dietary instruction over prior month&#xD;
&#xD;
          -  Considered by the treating physician(s) to be in otherwise stable clinical condition.&#xD;
&#xD;
          -  If patient is of childbearing potential, he/she will be willing to avoid pregnancy&#xD;
             during the study using an acceptable birth control method.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not considered by the treating physician(s) to be adherent with recommended dialysis&#xD;
             schedule and prescribed medications&#xD;
&#xD;
          -  Life expectancy &lt; 3 months&#xD;
&#xD;
          -  Dialysis-dependent for less than 6 months&#xD;
&#xD;
          -  Non-elective hospitalization in prior 3 months&#xD;
&#xD;
          -  Currently prescription of oral potassium supplements&#xD;
&#xD;
          -  In the prior 3 months, therapy with oral potassium-lowering medication&#xD;
&#xD;
          -  Underlying severe gastrointestinal disorders, including history of ischemic bowel.&#xD;
&#xD;
          -  Corrected serum calcium concentration &gt; 10.5 mg/dL in prior three months&#xD;
&#xD;
          -  Anticipated kidney transplant within the next 3 months&#xD;
&#xD;
          -  Prisoners or others who are involuntarily incarcerated or detained&#xD;
&#xD;
          -  Pregnant, breastfeeding, or considering pregnancy.&#xD;
&#xD;
          -  Participation in a clinical trial of an experimental treatment within the past 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John P Middleton, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DaVita Dialysis Sites</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hemodialysis</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>
    <mesh_term>Hyperkalemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Participant level data will not be shared.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03781089
org study id: Pro00088688
nct id: NCT03781089
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to determine whether once-daily dosing of patiromer will reduce
      the frequency of hyperkalemic episodes in ESRD (end stage renal disease) study participants
      who receive conventional hemodialysis (HD). The study objective is to determine if patiromer
      administered orally once a day with breakfast or lunch will reduce episodes of hyperkalemia
      in ESRD study participants who receive thrice-weekly HD.
This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice
      weekly HD schedule will be screened from retrospective review of clinical and laboratory
      parameters from our clinical practice group. A total of 40 study participants (randomized 1:1
      study drug: usual care) will be enrolled. Duration of study medication exposure will be 4
      weeks. The total duration of study, from enrollment until the end of the washout period will
      be 7 weeks.

      This is a proof of concept study, to determine whether administration of patiromer has the
      potential to change the risk category for ESRD patients who are on conventional HD schedules.
      In addition, the study will develop and pilot study procedures that could be implemented in a
      large-scale clinical trial. By nature of the limited size of the study, the power of the
      trial will be limited. Reducing serum potassium with the use of low dialysate potassium is
      actually associated with an increased risk of sudden cardiac death. Furthermore, HD patients
      already carry a high pill burden, and it is unclear if prescription of an additional oral
      medication will reduce the frequency of episodic hyperkalemia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice weekly HD schedule will be screened from retrospective review of clinical and laboratory parameters from our clinical practice group. A total of 40 patients (randomized 1:1 study drug: usual care) will be enrolled. Duration of study medication exposure will be 4 weeks. The total duration of study, from enrollment until the end of the washout period will be 7 weeks.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
masking description: The study is open-label and therefore the subjects, coordinators and investigators are not blinded to the intervention. Titration of the patiromer will require viewing of the serum potassium values. During the data analysis, however, personnel involved will remain blinded.
measure: Number of episodes of serum K ≥ 5.5 mEq/L
time frame: 4 weeks
description: To determine if patiromer administered orally once a day with the mid-day meal will reduce episodes of hyperkalemia in ESRD patients who receive thrice-weekly HemoDiaylsis
measure: Percent of patients with serum K > 5.5 mEq/L
time frame: 4 weeks
description: To determine the between-group differences in percent of patients with serum K > 5.5 mEq/L
measure: Average dose of patiromer that was given in treatment arm
time frame: 4 weeks
description: To determine the efficacy and dosing of patiromer in ESRD patients.
measure: Number of additional hemodialysis treatments due to hyperkalemia.
time frame: 4 weeks
description: To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia
measure: Number of significant arrhythmia events as detected with cardiac monitors in Week 4.
time frame: 4 weeks
description: To determine the between-group differences in pre-specified significant arrhythmia events as detected with cardiac monitors in Week 4.
measure: Difference percentage in serum albumin concentrations.
time frame: 4 weeks
description: To determine the between-group differences in serum albumin concentrations.
measure: Difference percentage in PTH concentrations.
time frame: 4 weeks
description: To determine the between-group differences in PTH concentrations.
measure: Number of patients who completed all study visits.
time frame: 4 weeks
description: To determine feasibility of a large-scale hemodialysis-based trial.
measure: Change percentage in serum potassium concentration two weeks after study drug is discontinued.
time frame: 6 weeks
description: To determine the change in serum potassium concentration two weeks after study drug is discontinued
measure: Change percentage in serum phosphorus concentration two weeks after study drug has been discontinued.
time frame: 6 weeks
description: To determine the change in serum phosphorus concentration two weeks after study drug has been discontinued
measure: Number of > 1000 PVC/24 hours.
time frame: 4 weeks
description: Presence of > 1000 PVC/24 hours
measure: Number of significant arrhythmias.
time frame: 4 weeks
description: The between-group and Week-0-to-Week-4-differences in significant arrhythmias will be evaluated.
arm group label: Patiromer Oral Powder Product
arm group type: Experimental
description: Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L.
arm group label: Usual care arm
arm group type: No Intervention
description: Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol
intervention type: Drug
intervention name: Patiromer Oral Powder Product
description: Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L. Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol
arm group label: Patiromer Oral Powder Product
other name: Valtressa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John P Middleton, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Hyperkalemia
sharing ipd: No
ipd description: Participant level data will not be shared.