xml: <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/NCT06038162</url>
    </required_header>
    <id_info>
      <org_study_id>69HCL22_0894</org_study_id>
      <nct_id>NCT06038162</nct_id>
    </id_info>
    <brief_title>Evaluation of Integrated Versus Parallel Connection for Renal Replacement Therapy in ECMO Patients</brief_title>
    <acronym>EPIC-ECMO</acronym>
    <official_title>Evaluation of Integrated Versus Parallel Continuous Renal Replacement Therapy Connection in ECMO Patients: a Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hospices Civils de Lyon</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Hospices Civils de Lyon</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Extracorporeal membrane oxygenation (ECMO) is an extra-corporeal assistance used in case of&#xD;
        respiratory or circulatory failure. In case of circulatory failure, ECMO is in the&#xD;
        veno-arterial configuration (VA-ECMO). VA-ECMO patients are at high risk of developing acute&#xD;
        kidney injury (AKI) and renal replacement therapy (RRT) may be needed in 50% of ECMO&#xD;
        patients. Although the administration of RRT in ECMO patients has major implications, no&#xD;
        specific recommendations are currently available. The 2020 Kidney Disease: Improving Global&#xD;
        Outcomes (KDIGO) international conference identified the evaluation of RRT in these ECMO&#xD;
        patients as a research priority.&#xD;
  &#xD;
        In 2023, the two main configurations used to administer RRT in ECMO patients are an&#xD;
        independent delivery on a separate vascular access (parallel connection) or an integration of&#xD;
        the RRT machine directly into the ECMO circuit (integrated connection). The integrated&#xD;
        connection may reduce infectious and bleeding complications associated with the use of a&#xD;
        second vascular access. However, it can expose the hemofilter and circuit to excessive&#xD;
        positive pressures that can trigger pressure alarms in the RRT machine and expose the patient&#xD;
        to a theoretical risk of air embolism or hemolysis. Furthermore, there is currently no robust&#xD;
        data comparing the hemofilter lifespan with the parallel or with the integrated connection,&#xD;
        although the filter lifespan is a crucial parameter to assess the quality of the RRT delivery&#xD;
        in the ICU. The investigators recently performed a survey of practices in this context of&#xD;
        ECMO patients. The investigators found that both strategies (parallel and integrated&#xD;
        connection) are widely used and can be seen as common patient care.&#xD;
  &#xD;
        The hypothesis tested in this study is the following: when RRT is integrated to the ECMO&#xD;
        circuit, the hemofilter lifespan is non inferior to the one when RRT is delivered on a&#xD;
        separate vascular access. Only VA-ECMO patients will be enrolled in this trial.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">September 2025</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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Hemofilter change rate</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether integrated RRT connection in VA-ECMO patients results in a non-inferior hemofilter change rate compared to the parallel connection.&#xD;
  The hemofilter change rate is defined as the number of hemofilter replacements observed during the period between the start and the end of the RRT session, normalized by the duration of the session.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of early hemofilter thromboses</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess if the integrated RRT connection is associated with a lower proportion of early hemofilter thromboses compared to the parallel connection: number of early hemofilter thromboses normalized by the number of hemofilters used. &quot;Early&quot; is defined as &lt; 24 hours of use.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of hemofilter thromboses</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess if the integrated RRT connection is associated with a lower proportion of hemofilter thromboses compared to the parallel connection: number of hemofilter thromboses normalized by the number of hemofilters used.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Down-time</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To compare the integrated RRT connection to the parallel connection in terms of duration of non-purification periods in relation to the total duration RRT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Renal function according to KDIGO stage</measure>
      <time_frame>At hospital discharge up to 60 days after admission</time_frame>
      <description>To assess renal function at hospital discharge or at day 60 after admission.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of infectious complications</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection reduces the number of infectious complications associated with the use of an additional vascular access.&#xD;
  The infection will be defined as catheter-related in case of documented bacteraemia with positive blood cultures with differential time to positivity or positive catheter culture with the same microorganism.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of bleeding complications</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection reduces bleeding complications associated with the use of an additional vascular access.&#xD;
  The occurrence of a bleeding syndrome is defined as a bleeding requiring transfusion with collection of the number of red blood cells transfused or requiring an invasive procedure (surgery, embolization), and defined or not as related to dialysis catheter placement or RRT connection to VA-ECMO.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of ECMO circuit thromboses</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection does not expose the ECMO circuit to a higher probability of thrombosis The occurrence of thrombosis on the ECMO circuit is defined as a thrombus on any part of the ECMO circuit requiring a change in the circuit or oxygenator, or on the oxygenator resulting in a deleterious effect on oxygenation, or resulting in significant fibrinolysis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of hemolysis</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection does not expose to a higher probability of hemolysis.&#xD;
  The occurrence of intravascular hemolysis is defined as the occurrence of significant hemolytic anemia.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of air embolism</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection does not expose the patient to a higher probability of air embolism.&#xD;
  The occurrence of an air embolism is defined as an embolic event with clinical impact of any kind, This occurence is related or not to the use of the dialysis catheter or the connection of the RRT to the VA-ECMO circuit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of days spent in intensive care unit</measure>
      <time_frame>Duration of RRT associated with VA-ECMO up to 60 days</time_frame>
      <description>To assess whether the integrated RRT connection modifies the intensive care unit length of stay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Death</measure>
      <time_frame>At 30 days</time_frame>
      <description>30-day mortality</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">158</enrollment>
    <condition>Venoarterial Extracorporeal Membrane Oxygenation</condition>
    <condition>Renal Replacement Therapy</condition>
    <condition>Acute Kidney Injury</condition>
    <arm_group>
      <arm_group_label>VA-ECMO patients with parallel connection</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients undergoing VA ECMO with indication for concomitant RRT, assigned to parallel connection group.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>VA-ECMO patients with integrated connection</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients undergoing VA ECMO with indication for concomitant RRT, assigned to integrated connection group.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Parallel connection</intervention_name>
      <description>The RRT machine is connected on a separate vascular access (dialysis catheter).</description>
      <arm_group_label>VA-ECMO patients with parallel connection</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Integrated connection</intervention_name>
      <description>A connection of the RRT machine with the input and output lines directly on the ECMO circuit.</description>
      <arm_group_label>VA-ECMO patients with integrated connection</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients between 18 and 75 years of age&#xD;
  &#xD;
            -  Patient on VA-ECMO who requires the initiation of continuous RRT during VA-ECMO&#xD;
               treatment&#xD;
  &#xD;
            -  Patient with a foreseeable length of stay in intensive care greater than 24 hours&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient who does not have a vascular capital allowing for the insertion of a new&#xD;
               dialysis catheter to administer RRT and therefore cannot be randomized to the parallel&#xD;
               connection group&#xD;
  &#xD;
            -  Pregnant, parturient, or breastfeeding women&#xD;
  &#xD;
            -  Patient deprived of liberty by a judicial or administrative decision&#xD;
  &#xD;
            -  Patient under psychiatric care&#xD;
  &#xD;
            -  Patient subject to a legal protection measure (guardianship, curators)&#xD;
  &#xD;
            -  Patient not affiliated to a social security system&#xD;
  &#xD;
            -  Patient participating in another interventional research study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Frank BIDAR, MD</last_name>
      <role>Study Chair</role>
      <affiliation>Hospices Civils de Lyon</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Frank BIDAR, MD</last_name>
      <phone>(33) 472 116 942</phone>
      <email>frank.bidar@chu-lyon.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Thomas RIMMELE, Professor MD</last_name>
      <phone>(33) 472 111 327</phone>
      <email>thomas.rimmele@chu-lyon.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>CHU de Bordeaux, GH Sud, Service d'anesthésie-réanimation cardiovasculaire, Hôpital cardiologique</name>
        <address>
          <city>Bordeaux</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Alexandre OUATTARA, Professor MD</last_name>
        <phone>(33) 557 656 866</phone>
        <email>alexandre.ouattara@chu-bordeaux.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>CHU de Clermont Ferrand, Pôle de médecine péri-opératoire/Chirurgie cardiaque, Hôpital Gabriel Montpied</name>
        <address>
          <city>Clermont-Ferrand</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Vedat ELJEZI, Professor MD</last_name>
        <phone>(33) 473 751 590</phone>
        <email>veljezi@chu-clermontferrand.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>CHU de Grenoble, Service de réanimation cardiovasculaire et thoracique, Pôle anesthésie réanimation, Hôpital Nord</name>
        <address>
          <city>Grenoble</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Géraldine DESSERTAINE, MD</last_name>
        <phone>(33) 476 767 588</phone>
        <email>Gdessertaine@chu-grenoble.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hospices Civils de Lyon, Service d'Anesthésie-Réanimation cardiovasculaire, Hôpital Louis Pradel</name>
        <address>
          <city>Lyon</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Jean-Luc FELLAHI, Professor MD</last_name>
        <phone>(33) 472 118 933</phone>
        <email>Jean-luc.fellahi@chu-lyon.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>CHU de Montpellier, Département d'anesthésie-réanimation, Pôle Cœur-poumons, Hôpital Arnaud de Villeneuve</name>
        <address>
          <city>Montpellier</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Philippe GAUDARD, MD</last_name>
        <phone>(33) 467 335 958</phone>
        <email>p-gaudard@chu-montpellier.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>APHP, Institut de Cardiologie, Service d'anesthésie-réanimation cardiovasculaire, Hôpital de la Pitié-Salpêtrière</name>
        <address>
          <city>Paris</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Adrien BOUGLE, MD</last_name>
        <phone>(33) 142 162 259</phone>
        <email>Adrien.bougle@aphp.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>APHP, Institut de cardiologie, Service de Médecine Intensive Réanimation, Hôpital Pitié-Salpêtrière</name>
        <address>
          <city>Paris</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Charles-Edouard LUYT, Professor MD</last_name>
        <phone>(33) 142 163 824</phone>
        <email>Charles-edouard.luyt@aphp.fr</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>CHU de Saint Etienne, Hôpital Bellevue, Service de Réanimation polyvalente et soins intensifs post-opératoires</name>
        <address>
          <city>Saint-Étienne</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Jérôme MOREL, Professor MD</last_name>
        <phone>(33) 477 828 329</phone>
        <email>Jerome.morel@chu-st-etienne.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>VA-ECMO</keyword>
    <keyword>RRT</keyword>
    <keyword>connection</keyword>
    <keyword>integrated</keyword>
    <keyword>parallel</keyword>
    <keyword>hemofilter</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Acute Kidney Injury</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06038162
  org study id: 69HCL22_0894
  nct id: NCT06038162
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Extracorporeal membrane oxygenation (ECMO) is an extra-corporeal assistance used in case of
        respiratory or circulatory failure. In case of circulatory failure, ECMO is in the
        veno-arterial configuration (VA-ECMO). VA-ECMO patients are at high risk of developing acute
        kidney injury (AKI) and renal replacement therapy (RRT) may be needed in 50% of ECMO
        patients. Although the administration of RRT in ECMO patients has major implications, no
        specific recommendations are currently available. The 2020 Kidney Disease: Improving Global
        Outcomes (KDIGO) international conference identified the evaluation of RRT in these ECMO
        patients as a research priority.
  
        In 2023, the two main configurations used to administer RRT in ECMO patients are an
        independent delivery on a separate vascular access (parallel connection) or an integration of
        the RRT machine directly into the ECMO circuit (integrated connection). The integrated
        connection may reduce infectious and bleeding complications associated with the use of a
        second vascular access. However, it can expose the hemofilter and circuit to excessive
        positive pressures that can trigger pressure alarms in the RRT machine and expose the patient
        to a theoretical risk of air embolism or hemolysis. Furthermore, there is currently no robust
        data comparing the hemofilter lifespan with the parallel or with the integrated connection,
        although the filter lifespan is a crucial parameter to assess the quality of the RRT delivery
        in the ICU. The investigators recently performed a survey of practices in this context of
        ECMO patients. The investigators found that both strategies (parallel and integrated
        connection) are widely used and can be seen as common patient care.
  
        The hypothesis tested in this study is the following: when RRT is integrated to the ECMO
        circuit, the hemofilter lifespan is non inferior to the one when RRT is delivered on a
        separate vascular access. Only VA-ECMO patients will be enrolled in this trial.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Hemofilter change rate
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether integrated RRT connection in VA-ECMO patients results in a non-inferior hemofilter change rate compared to the parallel connection.
  The hemofilter change rate is defined as the number of hemofilter replacements observed during the period between the start and the end of the RRT session, normalized by the duration of the session.
  measure: Proportion of early hemofilter thromboses
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess if the integrated RRT connection is associated with a lower proportion of early hemofilter thromboses compared to the parallel connection: number of early hemofilter thromboses normalized by the number of hemofilters used. "Early" is defined as < 24 hours of use.
  measure: Proportion of hemofilter thromboses
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess if the integrated RRT connection is associated with a lower proportion of hemofilter thromboses compared to the parallel connection: number of hemofilter thromboses normalized by the number of hemofilters used.
  measure: Down-time
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To compare the integrated RRT connection to the parallel connection in terms of duration of non-purification periods in relation to the total duration RRT.
  measure: Renal function according to KDIGO stage
  time frame: At hospital discharge up to 60 days after admission
  description: To assess renal function at hospital discharge or at day 60 after admission.
  measure: Number of infectious complications
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection reduces the number of infectious complications associated with the use of an additional vascular access.
  The infection will be defined as catheter-related in case of documented bacteraemia with positive blood cultures with differential time to positivity or positive catheter culture with the same microorganism.
  measure: Number of bleeding complications
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection reduces bleeding complications associated with the use of an additional vascular access.
  The occurrence of a bleeding syndrome is defined as a bleeding requiring transfusion with collection of the number of red blood cells transfused or requiring an invasive procedure (surgery, embolization), and defined or not as related to dialysis catheter placement or RRT connection to VA-ECMO.
  measure: Proportion of ECMO circuit thromboses
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection does not expose the ECMO circuit to a higher probability of thrombosis The occurrence of thrombosis on the ECMO circuit is defined as a thrombus on any part of the ECMO circuit requiring a change in the circuit or oxygenator, or on the oxygenator resulting in a deleterious effect on oxygenation, or resulting in significant fibrinolysis
  measure: Number of hemolysis
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection does not expose to a higher probability of hemolysis.
  The occurrence of intravascular hemolysis is defined as the occurrence of significant hemolytic anemia.
  measure: Number of air embolism
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection does not expose the patient to a higher probability of air embolism.
  The occurrence of an air embolism is defined as an embolic event with clinical impact of any kind, This occurence is related or not to the use of the dialysis catheter or the connection of the RRT to the VA-ECMO circuit.
  measure: Number of days spent in intensive care unit
  time frame: Duration of RRT associated with VA-ECMO up to 60 days
  description: To assess whether the integrated RRT connection modifies the intensive care unit length of stay
  measure: Death
  time frame: At 30 days
  description: 30-day mortality
  arm group label: VA-ECMO patients with parallel connection
  arm group type: Active Comparator
  description: Patients undergoing VA ECMO with indication for concomitant RRT, assigned to parallel connection group.
  arm group label: VA-ECMO patients with integrated connection
  arm group type: Active Comparator
  description: Patients undergoing VA ECMO with indication for concomitant RRT, assigned to integrated connection group.
  intervention type: Procedure
  intervention name: Parallel connection
  description: The RRT machine is connected on a separate vascular access (dialysis catheter).
  arm group label: VA-ECMO patients with parallel connection
  intervention type: Procedure
  intervention name: Integrated connection
  description: A connection of the RRT machine with the input and output lines directly on the ECMO circuit.
  arm group label: VA-ECMO patients with integrated connection
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Frank BIDAR, MD
  role: Study Chair
  affiliation: Hospices Civils de Lyon
  last name: Frank BIDAR, MD
  phone: (33) 472 116 942
  email: frank.bidar@chu-lyon.fr
  last name: Thomas RIMMELE, Professor MD
  phone: (33) 472 111 327
  email: thomas.rimmele@chu-lyon.fr
  facility: 
  contact: 
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  contact: 
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  country: France
  responsible party type: Sponsor
  mesh term: Acute Kidney Injury