<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/NCT03249532</url>
  </required_header>
  <id_info>
    <org_study_id>ABR 61210</org_study_id>
    <nct_id>NCT03249532</nct_id>
  </id_info>
  <brief_title>Effect of Dialysis Techniques on Blood Pressure and Cardiac Function During Dialysis</brief_title>
  <acronym>HOLLANT</acronym>
  <official_title>Effect of High-volume Online hemodiafiLtration on Intra-diaLytic hemodynAmic (iN)sTability and Cardiac Function in Chronic Hemodialysis Patients (the HOLLANT Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amsterdam UMC, location VUmc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Niercentrum aan de Amstel, Amstelveen, Netherlands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>B.Braun Avitum AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Amsterdam UMC, location VUmc</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>
      Online hemodiafiltration confers a reduced mortality risk. However, it is not clear why HDF&#xD;
      improved survival. To gain more insight in this issue, the effect of 4 dialysis techniques&#xD;
      (differing in dialysate temperature and the absence/presence of convective clearance) on&#xD;
      intradialytic hemodynamic stability and cardiac function will be investigated in a&#xD;
      prospective cross over trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the use of high permeable dialyzers, which combine diffusive with convective&#xD;
      clearance, the clinical outcome of hemodialysis (HD) patients remains poor. In post-dilution&#xD;
      online hemodiafiltration (denoted further on as HDF) diffusive clearance is similar to HD,&#xD;
      while the amount of convective transport is considerable increased. Recently, 4 randomized&#xD;
      controlled trails have been published which compared HD with HDF. Although the results of the&#xD;
      individual studies were inconclusive, a recent meta-analysis, using individual patient data&#xD;
      of these studies, showed a superior outcome for patients treated with HDF. The largest&#xD;
      mortality reduction was obtained in patients receiving the highest convection volume&#xD;
      (high-volume HDF [HV-HDF] &gt;23 L/1.73 m2/session): all-cause mortality [22% (95 % confidence&#xD;
      interval [CI] 2-38)], cardiovascular disease (CVD) mortality [31% (95 % CI 0-53)].&#xD;
&#xD;
      It is far from clear, however, why (HV)HDF is associated with an improved survival. Both long&#xD;
      term and short term effects may be involved. With respect to the latter, the intra-dialytic&#xD;
      removal of middle molecular weight (MMW) uremic retention products and a superior&#xD;
      bio-incompatibility (BI) profile may play a role. In addition, treatment with HDF may induce&#xD;
      less intra-dialytic hypotension (IDH) and less tissue injury. Enhanced removal of the MMW&#xD;
      substance FGF23 may reduce the intra-dialytic acute phase reaction (APR), which is regarded a&#xD;
      chief element of HD-induced BI. Other key components which may contribute to IDH and are&#xD;
      supposed to be alleviated by HDF, include dialysis-induced hypoxia and intra-dialytic&#xD;
      extracellular vesicle release. Patho-physiologically, IDH depends both on a decline in the&#xD;
      circulating blood volume and an impaired response to hypovolaemia. As a result, venous&#xD;
      return, cardiac output and peripheral vascular resistance are impaired. Since IDH is reduced&#xD;
      by HD with cool dialysate (C-HD), thermal factors may play an important role.&#xD;
&#xD;
      Microcirculatory dysfunction is a prominent feature of HD patients. Since IDH occurs in&#xD;
      20-30% of the sessions, any interference with an already abnormal perfusion may further&#xD;
      deteriorate the structure and function of vital organs, such as the brain, gut and heart.&#xD;
      HD-associated cardiomyopathy, which is considered a model of repetitive organ&#xD;
      ischemia-reperfusion injury, is superimposed on the cardiac changes resulting from the&#xD;
      various inflammatory and metabolic derangements of pre-dialysis kidney disease. As measured&#xD;
      by imaging techniques and biomarkers, HD induces a fall in cardiac perfusion and elicits&#xD;
      tissue injury. While cardiac MRI is considered the reference method for LV quantification,&#xD;
      intra-dialytic measurements can only be obtained in stable patients who can be safely&#xD;
      transferred to the radiology department. Echocardiography, though, can be performed in all&#xD;
      individuals at the bed-side, including hypotension-prone patients. Because of its superiority&#xD;
      over standard echocardiography, especially with respect to diastolic (dys)function, speckle&#xD;
      tracking echocardiography will be used in the present study.&#xD;
&#xD;
      As mentioned, the effect on long term survival is especially prominent when HV-HDF is&#xD;
      applied. Theoretically, HV-HDF is also the preferred treatment to circumvent dialysis-induced&#xD;
      IDH, and hence, to alleviate the repetitive intra-dialytic tissue damage. Therefore, the&#xD;
      following hypotheses will be tested:&#xD;
&#xD;
        1. intra-dialytic hemodynamic stability is better preserved during HV-HDF as compared to&#xD;
           standard (S)-HD, C-HD and low volume (LV)-HDF;&#xD;
&#xD;
        2. mainly as a result of a better intra-dialytic hemodynamic stability, the severity of&#xD;
           organ injury, especially the heart, is least evident during HV-HDF;&#xD;
&#xD;
        3. the mechanism of a better preserved intra-dialytic hemodynamic stability during HV-HDF&#xD;
           depends on its superior thermal balance and/or bio-incompatibility, clearance of MMW&#xD;
           substances, or a combination of these items.&#xD;
&#xD;
      Worldwide, however, (HV)HDF is only limited available. Since intradialytic hemodynamic&#xD;
      instability may contribute substantially to the poor clinical prospects of&#xD;
      end-stage-kidney-disease (ESKD) patients, these individuals may benefit from each maneuver&#xD;
      that minimizes the number and severity of intradialytic hypotensive episodes. Therefore, the&#xD;
      question which of the comparator treatments [(S)-HD, C-HD and LV-HDF] has the best&#xD;
      intradialytic hemodynamic stability, appears relevant as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Actual">February 15, 2021</completion_date>
  <primary_completion_date type="Actual">February 15, 2021</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>prospective, cross over, randomized order</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>treatment period will not be available to the assessors of secondary outcomes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>intradialytic hypotension</measure>
    <time_frame>up to 4 hours (= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>nadir in systolic blood pressure (SBP) of 90 mmHg for patient with predialysis SBP &lt;160mmHg and a nadir of 100 mmHg for patients with predialysis SBP ≥160 mmHg during treatment (blood pressure will be measured before and every 15 minutes after the start of dialysis during the treatment)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>diastolic dysfunction during treatment</measure>
    <time_frame>up to 4 hours (= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>speckle tracking echocardiography will be performed before, after 60 minutes of dialysis and after and after 3,5 hours</description>
  </secondary_outcome>
  <other_outcome>
    <measure>systolic blood pressure</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>change in systolic blood pressure (mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>diastolic blood pressure</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>change in diastolic blood pressure (mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>mean arterial blood pressure</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>change in mean arterial blood pressure (mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>pulse pressure</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>change in pulse pressure (systolic - diastolic blood pressure; mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>beat-to-beat blood pressure</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>change in beat-to-beat blood pressure (finger cuff; mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>heart rate</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>change in heart rate (finger cuff assessment)</description>
  </other_outcome>
  <other_outcome>
    <measure>stroke volume</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>change in stroke volume (finger cuff assessment)</description>
  </other_outcome>
  <other_outcome>
    <measure>cardiac output</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>change in cardiac output (finger cuff assessment)</description>
  </other_outcome>
  <other_outcome>
    <measure>total peripheral resistance</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>change in total peripheral resistance (finger cuff assessment)</description>
  </other_outcome>
  <other_outcome>
    <measure>number of sessions with reached target dry weight</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality</time_frame>
    <description>number of sessions with reached target dry weight (kg)</description>
  </other_outcome>
  <other_outcome>
    <measure>relative blood volume</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 2 treatments on each modality</time_frame>
    <description>relative blood volume (%) during dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>oxygen saturation</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 2 treatments on each modality</time_frame>
    <description>oxygen saturation in the arterial line of the extracorporeal system (%) during dialysis treatment; patients with central venous catheters and fistulas/grafts will be analyzed separately</description>
  </other_outcome>
  <other_outcome>
    <measure>oxygen partial pressure (pO2)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>pO2 in the arterial line of the extracorporeal system (mmHg or kiloPascal [kPa], assessed by a point of care device) during dialysis treatment; patients with central venous catheters and fistulas/grafts will be analyzed separately</description>
  </other_outcome>
  <other_outcome>
    <measure>change in creatine kinase (CK)-MB</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of cardiac damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in bacterial DNA in blood</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of gut ischemia, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in soluble CD14</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of gut ischemia, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in extracellular vesicles (EVs)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of endothelial damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in soluble intercellular adhesion molecule-1 (s-ICAM-1)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of endothelial damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in high sensitivity C-reactive protein (hs-CRP)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of inflammation, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in interleukin-6 (IL-6)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of inflammation, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>change in fibroblast growth factor-23 (FGF-23)</measure>
    <time_frame>up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality</time_frame>
    <description>marker of inflammation/mineral bone disease, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>End Stage Renal Disease (ESRD)</condition>
  <condition>Hemodialysis</condition>
  <condition>Hemodiafiltration</condition>
  <condition>Intradialytic Hypotension</condition>
  <condition>Diastolic Dysfunction</condition>
  <arm_group>
    <arm_group_label>standard hemodialysis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 0 Liters (L)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cool hemodialysis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>prescription of dialysate temperature: 35.5 degrees celsius prescription of convection volume: 0 L</description>
  </arm_group>
  <arm_group>
    <arm_group_label>low volume hemodiafiltration</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 15 L</description>
  </arm_group>
  <arm_group>
    <arm_group_label>high volume hemodiafiltration</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 25 L</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>standard hemodialysis</intervention_name>
    <description>hemodialysis with high-flux dialyzer; prescription of dialysate temperature: 36.5 degrees Celsius; convection volume: not applicable</description>
    <arm_group_label>cool hemodialysis</arm_group_label>
    <arm_group_label>high volume hemodiafiltration</arm_group_label>
    <arm_group_label>low volume hemodiafiltration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>cool hemodialysis</intervention_name>
    <description>hemodialysis with high-flux dialyzer; prescription of dialysate temperature: 35.5 degrees Celsius; convection volume: not applicable</description>
    <arm_group_label>high volume hemodiafiltration</arm_group_label>
    <arm_group_label>low volume hemodiafiltration</arm_group_label>
    <arm_group_label>standard hemodialysis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>low volume hemodiafiltration</intervention_name>
    <description>hemodiafiltration; prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 15 L</description>
    <arm_group_label>cool hemodialysis</arm_group_label>
    <arm_group_label>high volume hemodiafiltration</arm_group_label>
    <arm_group_label>standard hemodialysis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>high volume hemodiafiltration</intervention_name>
    <description>hemodiafiltration; prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 25 L</description>
    <arm_group_label>cool hemodialysis</arm_group_label>
    <arm_group_label>low volume hemodiafiltration</arm_group_label>
    <arm_group_label>standard hemodialysis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  treatment with HD or HDF 3 x per week during at least 4 hours for at least 2 months&#xD;
&#xD;
          -  ability to understand study procedures&#xD;
&#xD;
          -  willingness to provide informed consent&#xD;
&#xD;
          -  single pool Kt/V urea (spKt/Vurea) ≥ 1.2&#xD;
&#xD;
          -  achievement of blood flow of ≥360 ml/min and/or convection volume of &gt;23 Liter per&#xD;
             treatment during the run-in phase&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - current age &lt; 18 years&#xD;
&#xD;
          -  severe incompliance to dialysis procedure and accompanying prescriptions, especially&#xD;
             frequency and duration of dialysis treatment&#xD;
&#xD;
          -  life expectancy &lt; 3 months&#xD;
&#xD;
          -  participation in another clinical intervention trial&#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>Muriel PC Grooteman, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Amsterdam UMC, location VUmc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Antonius Ziekenhuis</name>
      <address>
        <city>Nieuwegein</city>
        <state>Utrecht</state>
        <zip>3435 CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Niercentrum aan de Amstel</name>
      <address>
        <city>Amstelveen</city>
        <zip>1186 AM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VUmc</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>November 28, 2021</last_update_submitted>
  <last_update_submitted_qc>November 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Amsterdam UMC, location VUmc</investigator_affiliation>
    <investigator_full_name>M.P.C. Grooteman</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03249532
org study id: ABR 61210
nct id: NCT03249532
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Online hemodiafiltration confers a reduced mortality risk. However, it is not clear why HDF
      improved survival. To gain more insight in this issue, the effect of 4 dialysis techniques
      (differing in dialysate temperature and the absence/presence of convective clearance) on
      intradialytic hemodynamic stability and cardiac function will be investigated in a
      prospective cross over trial.
Despite the use of high permeable dialyzers, which combine diffusive with convective
      clearance, the clinical outcome of hemodialysis (HD) patients remains poor. In post-dilution
      online hemodiafiltration (denoted further on as HDF) diffusive clearance is similar to HD,
      while the amount of convective transport is considerable increased. Recently, 4 randomized
      controlled trails have been published which compared HD with HDF. Although the results of the
      individual studies were inconclusive, a recent meta-analysis, using individual patient data
      of these studies, showed a superior outcome for patients treated with HDF. The largest
      mortality reduction was obtained in patients receiving the highest convection volume
      (high-volume HDF [HV-HDF] >23 L/1.73 m2/session): all-cause mortality [22% (95 % confidence
      interval [CI] 2-38)], cardiovascular disease (CVD) mortality [31% (95 % CI 0-53)].

      It is far from clear, however, why (HV)HDF is associated with an improved survival. Both long
      term and short term effects may be involved. With respect to the latter, the intra-dialytic
      removal of middle molecular weight (MMW) uremic retention products and a superior
      bio-incompatibility (BI) profile may play a role. In addition, treatment with HDF may induce
      less intra-dialytic hypotension (IDH) and less tissue injury. Enhanced removal of the MMW
      substance FGF23 may reduce the intra-dialytic acute phase reaction (APR), which is regarded a
      chief element of HD-induced BI. Other key components which may contribute to IDH and are
      supposed to be alleviated by HDF, include dialysis-induced hypoxia and intra-dialytic
      extracellular vesicle release. Patho-physiologically, IDH depends both on a decline in the
      circulating blood volume and an impaired response to hypovolaemia. As a result, venous
      return, cardiac output and peripheral vascular resistance are impaired. Since IDH is reduced
      by HD with cool dialysate (C-HD), thermal factors may play an important role.

      Microcirculatory dysfunction is a prominent feature of HD patients. Since IDH occurs in
      20-30% of the sessions, any interference with an already abnormal perfusion may further
      deteriorate the structure and function of vital organs, such as the brain, gut and heart.
      HD-associated cardiomyopathy, which is considered a model of repetitive organ
      ischemia-reperfusion injury, is superimposed on the cardiac changes resulting from the
      various inflammatory and metabolic derangements of pre-dialysis kidney disease. As measured
      by imaging techniques and biomarkers, HD induces a fall in cardiac perfusion and elicits
      tissue injury. While cardiac MRI is considered the reference method for LV quantification,
      intra-dialytic measurements can only be obtained in stable patients who can be safely
      transferred to the radiology department. Echocardiography, though, can be performed in all
      individuals at the bed-side, including hypotension-prone patients. Because of its superiority
      over standard echocardiography, especially with respect to diastolic (dys)function, speckle
      tracking echocardiography will be used in the present study.

      As mentioned, the effect on long term survival is especially prominent when HV-HDF is
      applied. Theoretically, HV-HDF is also the preferred treatment to circumvent dialysis-induced
      IDH, and hence, to alleviate the repetitive intra-dialytic tissue damage. Therefore, the
      following hypotheses will be tested:

        1. intra-dialytic hemodynamic stability is better preserved during HV-HDF as compared to
           standard (S)-HD, C-HD and low volume (LV)-HDF;

        2. mainly as a result of a better intra-dialytic hemodynamic stability, the severity of
           organ injury, especially the heart, is least evident during HV-HDF;

        3. the mechanism of a better preserved intra-dialytic hemodynamic stability during HV-HDF
           depends on its superior thermal balance and/or bio-incompatibility, clearance of MMW
           substances, or a combination of these items.

      Worldwide, however, (HV)HDF is only limited available. Since intradialytic hemodynamic
      instability may contribute substantially to the poor clinical prospects of
      end-stage-kidney-disease (ESKD) patients, these individuals may benefit from each maneuver
      that minimizes the number and severity of intradialytic hypotensive episodes. Therefore, the
      question which of the comparator treatments [(S)-HD, C-HD and LV-HDF] has the best
      intradialytic hemodynamic stability, appears relevant as well.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: prospective, cross over, randomized order
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: treatment period will not be available to the assessors of secondary outcomes.
measure: intradialytic hypotension
time frame: up to 4 hours (= one dialysis treatment); assessed during 3 treatments on each modality
description: nadir in systolic blood pressure (SBP) of 90 mmHg for patient with predialysis SBP <160mmHg and a nadir of 100 mmHg for patients with predialysis SBP ≥160 mmHg during treatment (blood pressure will be measured before and every 15 minutes after the start of dialysis during the treatment)
measure: diastolic dysfunction during treatment
time frame: up to 4 hours (= one dialysis treatment); assessed during 1 treatment on each modality
description: speckle tracking echocardiography will be performed before, after 60 minutes of dialysis and after and after 3,5 hours
measure: systolic blood pressure
time frame: up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality
description: change in systolic blood pressure (mmHg)
measure: diastolic blood pressure
time frame: up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality
description: change in diastolic blood pressure (mmHg)
measure: mean arterial blood pressure
time frame: up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality
description: change in mean arterial blood pressure (mmHg)
measure: pulse pressure
time frame: up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality
description: change in pulse pressure (systolic - diastolic blood pressure; mmHg)
measure: beat-to-beat blood pressure
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: change in beat-to-beat blood pressure (finger cuff; mmHg)
measure: heart rate
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: change in heart rate (finger cuff assessment)
measure: stroke volume
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: change in stroke volume (finger cuff assessment)
measure: cardiac output
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: change in cardiac output (finger cuff assessment)
measure: total peripheral resistance
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: change in total peripheral resistance (finger cuff assessment)
measure: number of sessions with reached target dry weight
time frame: up to 4 hours(= one dialysis treatment); assessed during 3 treatments on each modality
description: number of sessions with reached target dry weight (kg)
measure: relative blood volume
time frame: up to 4 hours(= one dialysis treatment); assessed during 2 treatments on each modality
description: relative blood volume (%) during dialysis treatment
measure: oxygen saturation
time frame: up to 4 hours(= one dialysis treatment); assessed during 2 treatments on each modality
description: oxygen saturation in the arterial line of the extracorporeal system (%) during dialysis treatment; patients with central venous catheters and fistulas/grafts will be analyzed separately
measure: oxygen partial pressure (pO2)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: pO2 in the arterial line of the extracorporeal system (mmHg or kiloPascal [kPa], assessed by a point of care device) during dialysis treatment; patients with central venous catheters and fistulas/grafts will be analyzed separately
measure: change in creatine kinase (CK)-MB
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of cardiac damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in bacterial DNA in blood
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of gut ischemia, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in soluble CD14
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of gut ischemia, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in extracellular vesicles (EVs)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of endothelial damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in soluble intercellular adhesion molecule-1 (s-ICAM-1)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of endothelial damage, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in high sensitivity C-reactive protein (hs-CRP)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of inflammation, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in interleukin-6 (IL-6)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of inflammation, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
measure: change in fibroblast growth factor-23 (FGF-23)
time frame: up to 4 hours(= one dialysis treatment); assessed during 1 treatment on each modality
description: marker of inflammation/mineral bone disease, assessment in blood from arterial line of extracorporeal circuit, before and after dialysis treatment
arm group label: standard hemodialysis
arm group type: Active Comparator
description: prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 0 Liters (L)
arm group label: cool hemodialysis
arm group type: Active Comparator
description: prescription of dialysate temperature: 35.5 degrees celsius prescription of convection volume: 0 L
arm group label: low volume hemodiafiltration
arm group type: Active Comparator
description: prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 15 L
arm group label: high volume hemodiafiltration
arm group type: Active Comparator
description: prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 25 L
intervention type: Device
intervention name: standard hemodialysis
description: hemodialysis with high-flux dialyzer; prescription of dialysate temperature: 36.5 degrees Celsius; convection volume: not applicable
arm group label: cool hemodialysis
arm group label: high volume hemodiafiltration
arm group label: low volume hemodiafiltration
intervention type: Device
intervention name: cool hemodialysis
description: hemodialysis with high-flux dialyzer; prescription of dialysate temperature: 35.5 degrees Celsius; convection volume: not applicable
arm group label: high volume hemodiafiltration
arm group label: low volume hemodiafiltration
arm group label: standard hemodialysis
intervention type: Device
intervention name: low volume hemodiafiltration
description: hemodiafiltration; prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 15 L
arm group label: cool hemodialysis
arm group label: high volume hemodiafiltration
arm group label: standard hemodialysis
intervention type: Device
intervention name: high volume hemodiafiltration
description: hemodiafiltration; prescription of dialysate temperature: 36.5 degrees celsius prescription of convection volume: 25 L
arm group label: cool hemodialysis
arm group label: low volume hemodiafiltration
arm group label: standard hemodialysis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Muriel PC Grooteman, MD PhD
role: Principal Investigator
affiliation: Amsterdam UMC, location VUmc
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Amsterdam UMC, location VUmc
investigator full name: M.P.C. Grooteman
investigator title: MD PhD
mesh term: Kidney Failure, Chronic
mesh term: Hypotension
sharing ipd: No