<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/NCT03303807</url>
  </required_header>
  <id_info>
    <org_study_id>P160701</org_study_id>
    <secondary_id>2016-A01689-42</secondary_id>
    <nct_id>NCT03303807</nct_id>
  </id_info>
  <brief_title>Correction by ECCO2-R of Hypercapnia in Patients With DVP in Moderate to Severe ARDS Under Protective Ventilation.</brief_title>
  <acronym>COVAP</acronym>
  <official_title>Study of Carbon Dioxide Removal to Alleviate Right Ventricule Dysfunction During Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Pulmonary vascular dysfunction (DVP) is associated with a pejorative prognosis during ARDS.&#xD;
      There is no specific therapeutic intervention to thwart it. Extracorporeal CO2 purification&#xD;
      (ECCO2-R) is a technique that has been very rapidly diffused and adopted in intensive care&#xD;
      since commercialization of the devices but, the formal clinical evaluation is insufficient.&#xD;
      It could significantly improve the prognosis of patients with both DVP and refractory&#xD;
      hypercapnia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, non-comparative, open-label, multicenter regional study, without&#xD;
      random drawing or blindfolding.&#xD;
&#xD;
      The primary objective of the study is the correction by ECCO2-R of hypercapnia in patients&#xD;
      with DVP in moderate to severe ARDS under protective ventilation.&#xD;
&#xD;
      The primary endpoint is the percentage of patients with hypercapnia correction (defined as a&#xD;
      20% decrease in PaCO2 at H2 of ECCO2-R initiation).&#xD;
&#xD;
      The secondary objectives are:&#xD;
&#xD;
        -  Demonstrate that ECCO2-R allows in hypercapnic ARDS and DVP patients to correct&#xD;
           hypercapnia with H6 and H24, improve DVP and hemodynamics, reduce alveolar dead space,&#xD;
           improvement of respiratory mechanics&#xD;
&#xD;
        -  Assess the tolerance of the evaluated technique.&#xD;
&#xD;
      The Secondary endpoints are:&#xD;
&#xD;
      - Relative change of capnia to H6 and H24 in relation to H0; proportion of patients with a&#xD;
      decrease of at least 20% of PaCO2 to H6 and H24; changes in echocardiographic indices;&#xD;
      hemodynamic parameters; alveolar deadspace and respiratory mechanics to H2, H6 and H24,&#xD;
      compared to H0; Complications, Mortality at reanimation discharge (or on D28 if this date&#xD;
      occurs before discharge of reanimation).&#xD;
&#xD;
      The intervention is based on the use of ECCO2-R (PrismaLung®, Prismaflex ® Baxter) in&#xD;
      eligible patients. ECCO2-R will be initiated as soon as possible after inclusion, for a&#xD;
      duration of at least 24 H (possibly prolonged up to 72 H at the decision of reanimator), by&#xD;
      jugular or femoral vein-venous.&#xD;
&#xD;
      The size of the catheters, the machine settings, in particular the blood flow and sweep will&#xD;
      be standardized according to the state of the art and the recommendations of the manufacturer&#xD;
&#xD;
      The ECO2R venous technique uses devices consisting of a monitor, an exchanger and a pump.&#xD;
&#xD;
        1. The PrismaLung® Kit (Baxter): Single-use EC-marked extracorporeal circuit intended for&#xD;
           use for at least 24 hours (maximum 72 hours).&#xD;
&#xD;
           The PrismaLung® kit is intended for use with the Prismaflex® monitor with software&#xD;
           version 8.10 or later and its support in conjunction with Prismaflex® single use&#xD;
           treatment sets.&#xD;
&#xD;
        2. The Prismaflex HP-X Set (Baxter): blood line set for extracorporeal blood circulation,&#xD;
           EC marked or the HF 1400® set (Baxter) (for extra-corporeal CO2 purification combined&#xD;
           with purification).&#xD;
&#xD;
        3. The Prismaflex® monitor (Baxter), EC marked, is used routinely in intensive care&#xD;
           (continuous extra-renal purification, therapeutic plasma exchange, haemoperfusion,&#xD;
           hemopurification).&#xD;
&#xD;
      So that each center has a dedicated monitor for research, this device will be provided by the&#xD;
      Baxter laboratory. The monitor will be equipped with a holder for the Prismalung kit marked&#xD;
      CE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">March 21, 2019</completion_date>
  <primary_completion_date type="Actual">February 25, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients with corrected hypercapnia</measure>
    <time_frame>at hour 2 (H2)</time_frame>
    <description>20% decrease in PaCO2 two hours after ECCO2-R initiation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative change of capnia at H6 and H24 after ECCO2-R</measure>
    <time_frame>at hour 6 (H6), at hour 24 (H24)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with a decrease of at least 20% of PaCO2 to H6 and H24</measure>
    <time_frame>H6, H24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in echocardiographic indices</measure>
    <time_frame>H2, H6, H24</time_frame>
    <description>Changes in echocardiographic indices at H2, H6 and H24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in hemodynamic parameters</measure>
    <time_frame>H2, H6, H24</time_frame>
    <description>Changes in hemodynamic parameters at H2, H6 and H24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in alveolar deadspace</measure>
    <time_frame>H2, H6, H24</time_frame>
    <description>Changes in alveolar deadspace at H2, H6 and H24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in respiratory mechanics</measure>
    <time_frame>H2, H6, H24</time_frame>
    <description>Changes in respiratory mechanics at H2, H6 and H24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of complications related to ECCO2-R technique</measure>
    <time_frame>ICU Discharge or day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of mortality</measure>
    <time_frame>ICU discharge or day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>Hypercapnia</condition>
  <arm_group>
    <arm_group_label>Extracorporeal CO2 removal</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)</intervention_name>
    <description>A low-flow CO2 removal device (Prismalung®, Baxter) will be used with a conventional renal replacement therapy (RRT) platform (Prismaflex®, Baxter). In patients already treated with continuous RRT because of renal failure or metabolic acidosis, the HF 1400® (Baxter) set will be used to combine RRT and decarboxylation. Gas flow through the gas exchanger will be set up to 10 L/min, with an oxygen concentration from 0.21 to 1 and a blood flow of 200-400 mL/min. Patients will be ventilated with a target tidal volume of 6 ml/kg (predicted body weight) and a target plateau pressure below 30 cmH2O.</description>
    <arm_group_label>Extracorporeal CO2 removal</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Moderate to severe ARDS according to the Berlin definition;&#xD;
&#xD;
          -  Pulmonary vascular dysfunction at echocardiography (pulmonary arterial hypertension,&#xD;
             right ventricular dilatation or dyskinesia of the interventricular septum);&#xD;
&#xD;
          -  Refractory hypercapnia, defined by a PaCO2 ≥48 mmHg in spite of the reduction of the&#xD;
             instrumental dead space and the increase of the respiratory rate.&#xD;
&#xD;
          -  Free and informed written consent for persons in a position to consent; consent of the&#xD;
             support person/parent/relative in case of incapacity to consent; inclusion in&#xD;
             emergency situations (Article L1122-1-2 of the CSP)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years;&#xD;
&#xD;
          -  Known pregnancy or breastfeeding;&#xD;
&#xD;
          -  Contra-indication to curative anticoagulation, thrombocytopenia &lt;50 G / L,&#xD;
             heparin-induced thrombocytopenia, known hypersensitivity to heparin or to compounds;&#xD;
&#xD;
          -  Femoral or jugular venous access impossible;&#xD;
&#xD;
          -  Refractory hypoxemia with indication at ECMO;&#xD;
&#xD;
          -  No affiliation to social security or beneficiary&#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>Armand Mekontso Dessap, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Henri Mondor Hospital</name>
      <address>
        <city>Creteil</city>
        <zip>94000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>July 1, 2019</last_update_submitted>
  <last_update_submitted_qc>July 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Extracorporeal CO2 removal (ECCO2-R)</keyword>
  <keyword>ARDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Hypercapnia</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/NCT03303807
org study id: P160701
secondary id: 2016-A01689-42
nct id: NCT03303807
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pulmonary vascular dysfunction (DVP) is associated with a pejorative prognosis during ARDS.
      There is no specific therapeutic intervention to thwart it. Extracorporeal CO2 purification
      (ECCO2-R) is a technique that has been very rapidly diffused and adopted in intensive care
      since commercialization of the devices but, the formal clinical evaluation is insufficient.
      It could significantly improve the prognosis of patients with both DVP and refractory
      hypercapnia.
This is a prospective, non-comparative, open-label, multicenter regional study, without
      random drawing or blindfolding.

      The primary objective of the study is the correction by ECCO2-R of hypercapnia in patients
      with DVP in moderate to severe ARDS under protective ventilation.

      The primary endpoint is the percentage of patients with hypercapnia correction (defined as a
      20% decrease in PaCO2 at H2 of ECCO2-R initiation).

      The secondary objectives are:

        -  Demonstrate that ECCO2-R allows in hypercapnic ARDS and DVP patients to correct
           hypercapnia with H6 and H24, improve DVP and hemodynamics, reduce alveolar dead space,
           improvement of respiratory mechanics

        -  Assess the tolerance of the evaluated technique.

      The Secondary endpoints are:

      - Relative change of capnia to H6 and H24 in relation to H0; proportion of patients with a
      decrease of at least 20% of PaCO2 to H6 and H24; changes in echocardiographic indices;
      hemodynamic parameters; alveolar deadspace and respiratory mechanics to H2, H6 and H24,
      compared to H0; Complications, Mortality at reanimation discharge (or on D28 if this date
      occurs before discharge of reanimation).

      The intervention is based on the use of ECCO2-R (PrismaLung®, Prismaflex ® Baxter) in
      eligible patients. ECCO2-R will be initiated as soon as possible after inclusion, for a
      duration of at least 24 H (possibly prolonged up to 72 H at the decision of reanimator), by
      jugular or femoral vein-venous.

      The size of the catheters, the machine settings, in particular the blood flow and sweep will
      be standardized according to the state of the art and the recommendations of the manufacturer

      The ECO2R venous technique uses devices consisting of a monitor, an exchanger and a pump.

        1. The PrismaLung® Kit (Baxter): Single-use EC-marked extracorporeal circuit intended for
           use for at least 24 hours (maximum 72 hours).

           The PrismaLung® kit is intended for use with the Prismaflex® monitor with software
           version 8.10 or later and its support in conjunction with Prismaflex® single use
           treatment sets.

        2. The Prismaflex HP-X Set (Baxter): blood line set for extracorporeal blood circulation,
           EC marked or the HF 1400® set (Baxter) (for extra-corporeal CO2 purification combined
           with purification).

        3. The Prismaflex® monitor (Baxter), EC marked, is used routinely in intensive care
           (continuous extra-renal purification, therapeutic plasma exchange, haemoperfusion,
           hemopurification).

      So that each center has a dedicated monitor for research, this device will be provided by the
      Baxter laboratory. The monitor will be equipped with a holder for the Prismalung kit marked
      CE.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Percentage of patients with corrected hypercapnia
time frame: at hour 2 (H2)
description: 20% decrease in PaCO2 two hours after ECCO2-R initiation
measure: Relative change of capnia at H6 and H24 after ECCO2-R
time frame: at hour 6 (H6), at hour 24 (H24)
measure: Proportion of patients with a decrease of at least 20% of PaCO2 to H6 and H24
time frame: H6, H24
measure: Changes in echocardiographic indices
time frame: H2, H6, H24
description: Changes in echocardiographic indices at H2, H6 and H24
measure: Changes in hemodynamic parameters
time frame: H2, H6, H24
description: Changes in hemodynamic parameters at H2, H6 and H24
measure: Changes in alveolar deadspace
time frame: H2, H6, H24
description: Changes in alveolar deadspace at H2, H6 and H24
measure: Changes in respiratory mechanics
time frame: H2, H6, H24
description: Changes in respiratory mechanics at H2, H6 and H24
measure: Number of complications related to ECCO2-R technique
time frame: ICU Discharge or day 28
measure: Percentage of mortality
time frame: ICU discharge or day 28
arm group label: Extracorporeal CO2 removal
arm group type: Other
description: Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)
intervention type: Device
intervention name: Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)
description: A low-flow CO2 removal device (Prismalung®, Baxter) will be used with a conventional renal replacement therapy (RRT) platform (Prismaflex®, Baxter). In patients already treated with continuous RRT because of renal failure or metabolic acidosis, the HF 1400® (Baxter) set will be used to combine RRT and decarboxylation. Gas flow through the gas exchanger will be set up to 10 L/min, with an oxygen concentration from 0.21 to 1 and a blood flow of 200-400 mL/min. Patients will be ventilated with a target tidal volume of 6 ml/kg (predicted body weight) and a target plateau pressure below 30 cmH2O.
arm group label: Extracorporeal CO2 removal
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Armand Mekontso Dessap, MD, PhD
role: Study Chair
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
mesh term: Hypercapnia