<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/NCT01698736</url>
  </required_header>
  <id_info>
    <org_study_id>EK 1540/2012</org_study_id>
    <nct_id>NCT01698736</nct_id>
  </id_info>
  <brief_title>ABO Blood Group Antibody Elimination by a Combination of Semiselective Immunoadsorption Therapy and Membrane Filtration</brief_title>
  <official_title>ABO Blood Group Antibody Elimination by a Combination of Semiselective Immunoadsorption Therapy and Membrane Filtration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fresenius Medical Care Deutschland GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  Recipient desensitization protocols were shown to enable successful living donor kidney&#xD;
           transplantation across major ABO blood group barriers. For extracorporeal depletion of&#xD;
           circulating ABO antibodies plasmapheresis or ABO blood group specific immunoadsorption&#xD;
           (IA) are most commonly used.&#xD;
&#xD;
        -  The efficiency of semiselective non-antigen specific IA in ABO-incompatible&#xD;
           transplantation is currently not well established. One potential drawback of&#xD;
           semiselective adsorbers could be an incomplete elimination of IgM.&#xD;
&#xD;
        -  This randomized controlled crossover trial was designed to clarify whether membrane&#xD;
           filtration, as an adjunct to semiselective IA, can substantially enhance elimination of&#xD;
           IgM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -Background and study aims&#xD;
&#xD;
      ABO-incompatible living donor kidney transplantation offers the possibility to expand the&#xD;
      donor pool by approximately 30%. A variety of different desensitization protocols were shown&#xD;
      to enable successful transplantation across major ABO barriers. In this context, apheresis&#xD;
      for antibody depletion represents the therapeutic mainstay. Two distinct technical&#xD;
      principles, plasmapheresis and ABO antigen-specific immunoadsorption, were shown to allow for&#xD;
      excellent short- and intermediate-term outcomes. A particular technical advantage of&#xD;
      immunoadsorption may be its high selectivity regarding antibody depletion, which precludes&#xD;
      major losses of essential plasma constituents, including coagulation factors and albumin,&#xD;
      even after treatment of large plasma volumes. Nevertheless, high treatment costs associated&#xD;
      with the use of ABO-specific columns (that are not approved for reuse) may limit their&#xD;
      widespread clinical application.&#xD;
&#xD;
      The efficiency of semi-selective immunoadsorption technologies regarding ABO antibody&#xD;
      depletion and recipient desensitization is less well established. Theoretically,&#xD;
      non-antigen-specific immunoglobulin depletion using protein A-, GAM peptide-, or anti-Ig&#xD;
      antibody-based adsorbers, could bring about several advantages, such as lower treatment costs&#xD;
      associated with the use of reusable twin columns, and the potential to simultaneously deplete&#xD;
      antibodies also against HLA antigens. A critical drawback, however, may be an evident&#xD;
      inefficiency regarding (ABO-specific) IgM depletion, and this could pose a considerable risk&#xD;
      of rejection.&#xD;
&#xD;
      One strategy to overcome the drawback of incomplete IgM depletion could be the use of&#xD;
      semiselective immunoadsorption combined with other antibody depletion technologies. In this&#xD;
      context, one attractive option could be an enhancement of antibody elimination by connecting&#xD;
      a membrane filter (cascade filter) to the immunoadsorption device. We propose to conduct an&#xD;
      open randomized crossover study that is designed to see if membrane filtration when applied&#xD;
      as an adjunct to semiselective immunoadsorption (GAM peptide adsorbers) is able to enhance&#xD;
      anti-ABO IgM elimination to an extent comparable to ABO antigen-specific immunoadsorption.&#xD;
      The results of this study, which will enrol 14 patients receiving IA treatment for clinical&#xD;
      indications outside the transplantation field, are expected to provide a valuable basis for&#xD;
      the use of combined apheresis approaches in the context of ABO-incompatible kidney&#xD;
      transplantation.&#xD;
&#xD;
      -Who can participate?&#xD;
&#xD;
      We are planning to recruit 14 adult patients (&gt;18 years, both genders eligible, healthy&#xD;
      volunteers not accepted) that are subject to regular routine IA therapy at &gt;1 weekly&#xD;
      intervals for clinical indications that are not related to ABO-incompatible transplantation&#xD;
      (antibody-mediated autoimmune disorders, such as systemic lupus erythematosus or myasthenia&#xD;
      gravis).&#xD;
&#xD;
      -What does the study involve?&#xD;
&#xD;
      For membrane filtration, we will use a membrane filter with documented capacity to eliminate&#xD;
      plasma IgM. The study will be conducted in a randomized crossover design (AB vs. BA design;&#xD;
      stratified randomization). Treatment consists in IA plus membrane filtration (A) or IA as the&#xD;
      sole treatment (B), respectively. The primary study endpoint is the percent reduction of ABO&#xD;
      blood group specific IgM. The study is powered to detect a 30% increase in IgM elimination.&#xD;
&#xD;
      -What are the possible benefits and risks of participating?&#xD;
&#xD;
      We do not expect any direct benefits for the study subjects. This pilot study, however, may&#xD;
      provide a valuable basis for a future trial evaluating the clinical impact of combined IA&#xD;
      plus membrane filtration in ABO incompatible transplantation. Potential risks include:&#xD;
      adverse reactions upon exposure to polysulfone (rash, pruritus, fever), reduction in&#xD;
      fibrinogen levels and eventually a transient increase in the risk of bleeding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</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>Percent reduction in flow cytometric ABO blood group specific IgM serum levels upon a single apheresis treatment</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent reduction in flow cytometric ABO blood group specific IgG serum levels upon a single apheresis treatment</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Effect on titers of ABO blood group specific IgG (indirect Coombs test)</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect on titers of ABO blood group specific IgM (direct agglutination test)</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect on concentrations of total serum IgG</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect on concentrations of total serum IgM</measure>
    <time_frame>Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Immunology</condition>
  <arm_group>
    <arm_group_label>Semiselective IA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Semiselective immunoadsorption (GAM peptide adsorber)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Semiselective IA + membrane filtration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Semiselective immunoadsorption (GAM peptide adsorber) in combination with membrane filtration</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Membrane filtration</intervention_name>
    <description>Membrane filtration (Polysulfone)</description>
    <arm_group_label>Semiselective IA + membrane filtration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Semiselective IA</intervention_name>
    <description>Semiselective immunoadsorption (GAM peptide adsorber)</description>
    <arm_group_label>Semiselective IA</arm_group_label>
    <arm_group_label>Semiselective IA + membrane filtration</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18a&#xD;
&#xD;
          -  Blood group A, B or O&#xD;
&#xD;
          -  Regular IA treatment for a disease not related to transplantation&#xD;
&#xD;
          -  Use of semiselective IA with GAM peptide adsorbers&#xD;
&#xD;
          -  IA treatment interval ≥ 7 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age ≤ 18a&#xD;
&#xD;
          -  Blood group AB (no isoagglutinins)&#xD;
&#xD;
          -  No signed consent&#xD;
&#xD;
          -  Pregnancy or breast feeding women (exclusion of pregnancy with pregnancy test)&#xD;
&#xD;
          -  Severe disease precluding immunoglobulin elimination by IA (e.g. severe infection)&#xD;
&#xD;
          -  Elevated risk of bleeding or coagulation disorders that make systemic anticoagulation&#xD;
             with heparin impossible&#xD;
&#xD;
          -  Hypersensitivity to heparin or HIT&#xD;
&#xD;
          -  Hypersensitivity to polysulfone&#xD;
&#xD;
          -  Participation in other clinical study&#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>Georg Böhmig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Nephrology, Medical University of Vienna</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>Wahrmann M, Schiemann M, Marinova L, Kormoczi GF, Derfler K, Fehr T, Stussi G, Bohmig GA. Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption. Nephrol Dial Transplant. 2012 May;27(5):2122-9. doi: 10.1093/ndt/gfr610. Epub 2011 Nov 15.</citation>
    <PMID>22086972</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>January 15, 2018</last_update_submitted>
  <last_update_submitted_qc>January 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Farsad Eskandary</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>ABO isoagglutinins</keyword>
  <keyword>ABO incompatible transplantation</keyword>
  <keyword>immunoadsorption</keyword>
  <keyword>membrane filtration</keyword>
  <keyword>plasmapheresis</keyword>
  <!-- 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/NCT01698736
org study id: EK 1540/2012
nct id: NCT01698736
lead sponsor: 
collaborator: 
has dmc: Yes
-  Recipient desensitization protocols were shown to enable successful living donor kidney
           transplantation across major ABO blood group barriers. For extracorporeal depletion of
           circulating ABO antibodies plasmapheresis or ABO blood group specific immunoadsorption
           (IA) are most commonly used.

        -  The efficiency of semiselective non-antigen specific IA in ABO-incompatible
           transplantation is currently not well established. One potential drawback of
           semiselective adsorbers could be an incomplete elimination of IgM.

        -  This randomized controlled crossover trial was designed to clarify whether membrane
           filtration, as an adjunct to semiselective IA, can substantially enhance elimination of
           IgM.
-Background and study aims

      ABO-incompatible living donor kidney transplantation offers the possibility to expand the
      donor pool by approximately 30%. A variety of different desensitization protocols were shown
      to enable successful transplantation across major ABO barriers. In this context, apheresis
      for antibody depletion represents the therapeutic mainstay. Two distinct technical
      principles, plasmapheresis and ABO antigen-specific immunoadsorption, were shown to allow for
      excellent short- and intermediate-term outcomes. A particular technical advantage of
      immunoadsorption may be its high selectivity regarding antibody depletion, which precludes
      major losses of essential plasma constituents, including coagulation factors and albumin,
      even after treatment of large plasma volumes. Nevertheless, high treatment costs associated
      with the use of ABO-specific columns (that are not approved for reuse) may limit their
      widespread clinical application.

      The efficiency of semi-selective immunoadsorption technologies regarding ABO antibody
      depletion and recipient desensitization is less well established. Theoretically,
      non-antigen-specific immunoglobulin depletion using protein A-, GAM peptide-, or anti-Ig
      antibody-based adsorbers, could bring about several advantages, such as lower treatment costs
      associated with the use of reusable twin columns, and the potential to simultaneously deplete
      antibodies also against HLA antigens. A critical drawback, however, may be an evident
      inefficiency regarding (ABO-specific) IgM depletion, and this could pose a considerable risk
      of rejection.

      One strategy to overcome the drawback of incomplete IgM depletion could be the use of
      semiselective immunoadsorption combined with other antibody depletion technologies. In this
      context, one attractive option could be an enhancement of antibody elimination by connecting
      a membrane filter (cascade filter) to the immunoadsorption device. We propose to conduct an
      open randomized crossover study that is designed to see if membrane filtration when applied
      as an adjunct to semiselective immunoadsorption (GAM peptide adsorbers) is able to enhance
      anti-ABO IgM elimination to an extent comparable to ABO antigen-specific immunoadsorption.
      The results of this study, which will enrol 14 patients receiving IA treatment for clinical
      indications outside the transplantation field, are expected to provide a valuable basis for
      the use of combined apheresis approaches in the context of ABO-incompatible kidney
      transplantation.

      -Who can participate?

      We are planning to recruit 14 adult patients (>18 years, both genders eligible, healthy
      volunteers not accepted) that are subject to regular routine IA therapy at >1 weekly
      intervals for clinical indications that are not related to ABO-incompatible transplantation
      (antibody-mediated autoimmune disorders, such as systemic lupus erythematosus or myasthenia
      gravis).

      -What does the study involve?

      For membrane filtration, we will use a membrane filter with documented capacity to eliminate
      plasma IgM. The study will be conducted in a randomized crossover design (AB vs. BA design;
      stratified randomization). Treatment consists in IA plus membrane filtration (A) or IA as the
      sole treatment (B), respectively. The primary study endpoint is the percent reduction of ABO
      blood group specific IgM. The study is powered to detect a 30% increase in IgM elimination.

      -What are the possible benefits and risks of participating?

      We do not expect any direct benefits for the study subjects. This pilot study, however, may
      provide a valuable basis for a future trial evaluating the clinical impact of combined IA
      plus membrane filtration in ABO incompatible transplantation. Potential risks include:
      adverse reactions upon exposure to polysulfone (rash, pruritus, fever), reduction in
      fibrinogen levels and eventually a transient increase in the risk of bleeding.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent reduction in flow cytometric ABO blood group specific IgM serum levels upon a single apheresis treatment
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
measure: Percent reduction in flow cytometric ABO blood group specific IgG serum levels upon a single apheresis treatment
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
measure: Effect on titers of ABO blood group specific IgG (indirect Coombs test)
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
measure: Effect on titers of ABO blood group specific IgM (direct agglutination test)
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
measure: Effect on concentrations of total serum IgG
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
measure: Effect on concentrations of total serum IgM
time frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
arm group label: Semiselective IA
arm group type: Active Comparator
description: Semiselective immunoadsorption (GAM peptide adsorber)
arm group label: Semiselective IA + membrane filtration
arm group type: Experimental
description: Semiselective immunoadsorption (GAM peptide adsorber) in combination with membrane filtration
intervention type: Device
intervention name: Membrane filtration
description: Membrane filtration (Polysulfone)
arm group label: Semiselective IA + membrane filtration
intervention type: Device
intervention name: Semiselective IA
description: Semiselective immunoadsorption (GAM peptide adsorber)
arm group label: Semiselective IA
arm group label: Semiselective IA + membrane filtration
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Georg Böhmig, MD
role: Principal Investigator
affiliation: Department of Nephrology, Medical University of Vienna
facility: 
country: Austria
citation: Wahrmann M, Schiemann M, Marinova L, Kormoczi GF, Derfler K, Fehr T, Stussi G, Bohmig GA. Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption. Nephrol Dial Transplant. 2012 May;27(5):2122-9. doi: 10.1093/ndt/gfr610. Epub 2011 Nov 15.
PMID: 22086972
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Farsad Eskandary
investigator title: MD