<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/NCT03288922</url>
  </required_header>
  <id_info>
    <org_study_id>291/58</org_study_id>
    <nct_id>NCT03288922</nct_id>
  </id_info>
  <brief_title>Protein-bound Toxin Removal Between Limited Blood Flow Super High-flux Online HDF and High-Efficiency Online HDF</brief_title>
  <official_title>Comparison of Protein-bound Toxins Removals Between Limited Blood Flow Online Hemodiafiltration Using Super High-flux Dialyzer and High-Efficiency Online Hemodiafiltration With High-flux Dialyzer: An Randomized Crossover Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chulalongkorn University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chulalongkorn University</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>
      High-efficiency post-dilution online hemodiafiltration (OL-HDF) using high-flux dialyzer and&#xD;
      requiring high blood flow rate (BF ≥400 mL/min) has been reported to enhance protein-bound&#xD;
      toxin and middle molecular toxin removal and improve patient survival. Unfortunately, the&#xD;
      majority of patients could not reach that high BF because of vascular access issue. This&#xD;
      randomized crossover study was conducted to compare these uremic toxin removals between the&#xD;
      new modality (limited BF OL-HDF with super high-flux dialyzer) and the control&#xD;
      (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality&#xD;
      or control for 2 weeks before crossover to the other modality for another 2 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Elevated protein-bound toxins including p-cresol (pCS) and indoxyl sulfate (IDS) as well as&#xD;
      middle-molecular toxins such as beta2-microglobulin (B2M) which could not be removed by&#xD;
      hemodialysis (HD) are obviously correlated with high mortality. High-efficiency post-dilution&#xD;
      online hemodiafiltration (OL-HDF) using high-flux dialyzer and requiring high blood flow rate&#xD;
      (BF ≥400 mL/min) has been reported to enhance pCS, IDS, and B2M removal and improve patient&#xD;
      survival. Unfortunately, the majority of patients could not reach that high BF because of&#xD;
      vascular access issue. We innovated the OL-HDF modality for this limited BF situation by&#xD;
      integrating the novel super high-flux membrane dialyzer (SHF; PES-17Dα, Nipro Corporation,&#xD;
      Japan) into pre-dilution OL-HDF. This randomized crossover study was conducted to compare the&#xD;
      uremic toxin removals between the new modality (limited BF OL-HDF with SHF) and the control&#xD;
      (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality&#xD;
      or control for 2 weeks before crossover to the other modality for another 2 weeks. Removals&#xD;
      of pCS and IDS as well as small and middle molecule toxins were compared. The pCS and IDS&#xD;
      were measured by high performance liquid chromatography. The dialysate albumin loss and&#xD;
      patient safety were also monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">October 2017</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pCS percentage of reduction ratio</measure>
    <time_frame>At time 0-hour and 4-hour of the study online hemodiafiltration session</time_frame>
    <description>Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. pCS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>IDS percentage of reduction ratio</measure>
    <time_frame>At time 0-hour and 4-hour of the study online hemodiafiltration session</time_frame>
    <description>Blood samples were taken from patients before and at the end of 4-hour in the first session of each modality. IDS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beta2-microglobulin percentage of reduction ratio</measure>
    <time_frame>At time 0-hour and 4-hour of the study online hemodiafiltration session</time_frame>
    <description>Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. The percentage of reduction ratio were calculated from the before and ending samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Albumin loss in spent dialysate</measure>
    <time_frame>During 4 hours of online hemodiafiltration session</time_frame>
    <description>Continuous sampling of spent effluent dialysate and ultrafiltrate were carried out with a collection pump inserted into the effluent outlet line via a special connector for total albumin loss determination.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>End-stage Renal Disease</condition>
  <condition>Hemodialysis</condition>
  <arm_group>
    <arm_group_label>Limited BF OL-HDF with SHF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Limited blood flow pre-dilution online hemodiafiltration using super high-flux dialyzer which had larger pore size than standard high-flux dialyzer was assigned as the new intervention to compare the efficacy of protein-bound toxin removals with the control period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-efficiency OL-HDF</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>High-efficiency post-dilution online hemodiafiltration using standard high-flux dialyzer was assigned as the control period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Limited BF OL-HDF with SHF</intervention_name>
    <description>The new modality &quot;Limited BF OL-HDF with SHF&quot; were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 300 ml/min and the total dialysis fluid flow rate was 800 ml/min which included pre-filter substitution rate of 150 ml/min. The super high-flux dialyzer was PES-17Dα from Nipro Corporation, Japan which contains 1.7 m2 hollow fiber polyethersulfone membrane (ultrafiltration coefficient 80 ml/h/mmHg; urea clearance 267 ml/min, Qb 300 ml/min and Qd 500ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.</description>
    <arm_group_label>Limited BF OL-HDF with SHF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>High-efficiency OL-HDF</intervention_name>
    <description>The controlled modality &quot;High-efficiency OL-HDF&quot; were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 400 ml/min and the total dialysis fluid flow rate was 800 ml/min which included post-filter substitution rate of 100 ml/min. The standard high-flux dialyzer that was used was HF80s from Fresenius Medical Care, Germany contains 1.8 m2 hollow fiber polysulfone membrane (ultrafiltration coefficient 55 ml/h/mmHg; urea clearance 248 ml/min, Qb 300ml/min and Qd 500 ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.</description>
    <arm_group_label>High-efficiency OL-HDF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  End-stage renal disease patients treated with thrice-a-week OL-HDF for at least 6&#xD;
             months&#xD;
&#xD;
          -  Residual urine &lt; 100 mL/day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active cardiovascular disease&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast-feeding&#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>Khajohn Tiranathanagul, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chulalongkorn University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Wanjak Pongsittisak</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chulalongkorn University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chulalongkorn Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>January 23, 2018</last_update_submitted>
  <last_update_submitted_qc>January 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chulalongkorn University</investigator_affiliation>
    <investigator_full_name>Khajohn Tiranathanagul</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Online Hemodiafiltration</keyword>
  <keyword>Super high-flux dialyzer</keyword>
  <keyword>Protein-bound uremic toxin</keyword>
  <keyword>P-cresol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <!-- 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/NCT03288922
org study id: 291/58
nct id: NCT03288922
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
High-efficiency post-dilution online hemodiafiltration (OL-HDF) using high-flux dialyzer and
      requiring high blood flow rate (BF ≥400 mL/min) has been reported to enhance protein-bound
      toxin and middle molecular toxin removal and improve patient survival. Unfortunately, the
      majority of patients could not reach that high BF because of vascular access issue. This
      randomized crossover study was conducted to compare these uremic toxin removals between the
      new modality (limited BF OL-HDF with super high-flux dialyzer) and the control
      (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality
      or control for 2 weeks before crossover to the other modality for another 2 weeks.
Elevated protein-bound toxins including p-cresol (pCS) and indoxyl sulfate (IDS) as well as
      middle-molecular toxins such as beta2-microglobulin (B2M) which could not be removed by
      hemodialysis (HD) are obviously correlated with high mortality. High-efficiency post-dilution
      online hemodiafiltration (OL-HDF) using high-flux dialyzer and requiring high blood flow rate
      (BF ≥400 mL/min) has been reported to enhance pCS, IDS, and B2M removal and improve patient
      survival. Unfortunately, the majority of patients could not reach that high BF because of
      vascular access issue. We innovated the OL-HDF modality for this limited BF situation by
      integrating the novel super high-flux membrane dialyzer (SHF; PES-17Dα, Nipro Corporation,
      Japan) into pre-dilution OL-HDF. This randomized crossover study was conducted to compare the
      uremic toxin removals between the new modality (limited BF OL-HDF with SHF) and the control
      (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality
      or control for 2 weeks before crossover to the other modality for another 2 weeks. Removals
      of pCS and IDS as well as small and middle molecule toxins were compared. The pCS and IDS
      were measured by high performance liquid chromatography. The dialysate albumin loss and
      patient safety were also monitored.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pCS percentage of reduction ratio
time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session
description: Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. pCS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.
measure: IDS percentage of reduction ratio
time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session
description: Blood samples were taken from patients before and at the end of 4-hour in the first session of each modality. IDS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.
measure: Beta2-microglobulin percentage of reduction ratio
time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session
description: Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. The percentage of reduction ratio were calculated from the before and ending samples.
measure: Albumin loss in spent dialysate
time frame: During 4 hours of online hemodiafiltration session
description: Continuous sampling of spent effluent dialysate and ultrafiltrate were carried out with a collection pump inserted into the effluent outlet line via a special connector for total albumin loss determination.
arm group label: Limited BF OL-HDF with SHF
arm group type: Experimental
description: Limited blood flow pre-dilution online hemodiafiltration using super high-flux dialyzer which had larger pore size than standard high-flux dialyzer was assigned as the new intervention to compare the efficacy of protein-bound toxin removals with the control period.
arm group label: High-efficiency OL-HDF
arm group type: Active Comparator
description: High-efficiency post-dilution online hemodiafiltration using standard high-flux dialyzer was assigned as the control period.
intervention type: Procedure
intervention name: Limited BF OL-HDF with SHF
description: The new modality "Limited BF OL-HDF with SHF" were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 300 ml/min and the total dialysis fluid flow rate was 800 ml/min which included pre-filter substitution rate of 150 ml/min. The super high-flux dialyzer was PES-17Dα from Nipro Corporation, Japan which contains 1.7 m2 hollow fiber polyethersulfone membrane (ultrafiltration coefficient 80 ml/h/mmHg; urea clearance 267 ml/min, Qb 300 ml/min and Qd 500ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.
arm group label: Limited BF OL-HDF with SHF
intervention type: Procedure
intervention name: High-efficiency OL-HDF
description: The controlled modality "High-efficiency OL-HDF" were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 400 ml/min and the total dialysis fluid flow rate was 800 ml/min which included post-filter substitution rate of 100 ml/min. The standard high-flux dialyzer that was used was HF80s from Fresenius Medical Care, Germany contains 1.8 m2 hollow fiber polysulfone membrane (ultrafiltration coefficient 55 ml/h/mmHg; urea clearance 248 ml/min, Qb 300ml/min and Qd 500 ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.
arm group label: High-efficiency OL-HDF
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Khajohn Tiranathanagul, MD
role: Principal Investigator
affiliation: Chulalongkorn University
last name: Wanjak Pongsittisak
role: Principal Investigator
affiliation: Chulalongkorn University
facility: 
country: Thailand
responsible party type: Principal Investigator
investigator affiliation: Chulalongkorn University
investigator full name: Khajohn Tiranathanagul
investigator title: Associate Professor
mesh term: Kidney Failure, Chronic