<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/NCT03004885</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A01523-48</org_study_id>
    <nct_id>NCT03004885</nct_id>
  </id_info>
  <brief_title>Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung</brief_title>
  <acronym>PROVAP</acronym>
  <official_title>Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hôpital Européen Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hôpital Européen Marseille</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>
      Acute Respiratory Distress Syndrome (ARDS) still remains associated with a mortality rate of&#xD;
      30 - 45 % despite improvement in mechanical ventilation. Driving pressure, defined as the&#xD;
      difference between the end-inspiratory and the end-expiratory airway pressure, appears as an&#xD;
      important factor contributing to mortality in patients with the ARDS. In patients already&#xD;
      receiving a conventional tidal volume of 6 ml/kg predicted body weight (PBW), a driving&#xD;
      pressure ≥ 14 cmH2O increases the risk of death in the hospital. One mean to lower the&#xD;
      driving pressure is to decrease the tidal volume such that from 6 to 4 ml/kg predicted body&#xD;
      weight. However, this strategy promotes hypercarbia by reducing the alveolar ventilation,&#xD;
      providing the respiratory rate is constant. In this setting, implementing an extracorporeal&#xD;
      CO2 removal (ECCO2R) therapy may offset the associated hypercarbia. The investigators have&#xD;
      previously demonstrated that combining a membrane oxygenator within an hemofiltration circuit&#xD;
      provides efficacious low flow ECCO2R on a renal replacement therapy monitor. In this study,&#xD;
      we thought to investigate the efficacy of the PrismaLung stand-alone therapy. Using a&#xD;
      PrismaFlex monitor and a HP-X circuit, a neonatal membrane oxygenator (PrismaLung) is used to&#xD;
      provide decarboxylation without renal replacement therapy. The study will consist in three&#xD;
      periods:&#xD;
&#xD;
        -  The first period will address the efficacy of the PrismaLung device at tidal volume of 6&#xD;
           and 4 ml/kg PBW using an off-on-off design.&#xD;
&#xD;
        -  The second part of the study will investigate the effect of varying the sweep gas flow&#xD;
           and the mixture of the sweep gas on the CO2 removal rate (random order).&#xD;
&#xD;
        -  The third part will compare three ventilatory strategies applied in a cross-over design&#xD;
           :&#xD;
&#xD;
             1. Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure&#xD;
                (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).&#xD;
&#xD;
             2. Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure&#xD;
                between 23 - 25 cmH2O.&#xD;
&#xD;
             3. Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table&#xD;
                (ARMA).&#xD;
&#xD;
      Each strategies will be apply in a random order for a duration of 22 hours. Pulmonary&#xD;
      inflammatory and fibrosis pathway will be assess before and after each period using&#xD;
      bronchoalveolar lavage (BAL) samples. Systemic inflammatory cytokines will also be&#xD;
      investigate. Main measurements will include respiratory mechanics, transpulmonary pressure,&#xD;
      work of breathing, end-expiratory lung volume and tidal ventilation using electrical&#xD;
      impedance tomography.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient CO2 removal obtained with the PrismaLung membrane oxygenator&#xD;
  </why_stopped>
  <start_date type="Actual">October 12, 2017</start_date>
  <completion_date type="Actual">December 20, 2017</completion_date>
  <primary_completion_date type="Actual">October 13, 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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in PaCO2</measure>
    <time_frame>15 min after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW (during the first part of the study).</time_frame>
    <description>20 % decrease in PaCO2 after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW versus 4 ml/kg PBW without ECCO2R.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PaCO2</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Arterial blood gas</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CO2 removal rate</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Using both the blood side and the gas side equation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory mechanics work of breathing</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transpulmonary pressure</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Work of breathing</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EIT</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Electrical Impedance Tomography using BB² (Swisstom)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EELV</measure>
    <time_frame>q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>End expiratory Lung volume using nitrogen wash-in wash-out method (Engstrom GE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Cytokines</measure>
    <time_frame>Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Elisa using plasma samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Cytokines</measure>
    <time_frame>Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>Elisa using BAL samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Type III Procollagen</measure>
    <time_frame>Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>RIA using plasma and BAL samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Inflammatory and Fibrotic pathway</measure>
    <time_frame>Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.</time_frame>
    <description>mRNA</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma Free Hemoglobin</measure>
    <time_frame>q24 h, up to 72 h</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Haptoglobin</measure>
    <time_frame>q24 h, up to 72 h</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Lacticodéshydrogenase (LDH)</measure>
    <time_frame>q24 h, up to 72 h</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>schizocytes</measure>
    <time_frame>q24 h, up to 72 h</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Bilirubin</measure>
    <time_frame>q24 h, up to 72 h</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Minimal Distension</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tidal volume 4 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maximal Recruitment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain plateau pressure between 23 - 25 cmH2O + ECCO2R</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tidal volume 6 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PrismaLung</intervention_name>
    <description>Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator</description>
    <arm_group_label>Maximal Recruitment</arm_group_label>
    <arm_group_label>Minimal Distension</arm_group_label>
    <arm_group_label>Standard</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ARDS moderate or severe (Berlin criteria)&#xD;
&#xD;
          -  Onset &lt; 48 h&#xD;
&#xD;
          -  Driving pressure ≥ 14 cmH2O&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lack of consent or social protection&#xD;
&#xD;
          -  Chronic respiratory failure (requiring Oxygen or NIPPV)&#xD;
&#xD;
          -  Severe hypoxemia: PaO2/FIO2 &lt; 100 with PEEP ≥ 18 cmH2O AND FIO2 = 1&#xD;
&#xD;
          -  Acute Renal Failure requiring RRT&#xD;
&#xD;
          -  DNR order or death expected within the next 72 hours&#xD;
&#xD;
          -  Planned surgery or out-of-ICU transportation expected within the next 72 hours&#xD;
&#xD;
          -  Heparin allergy&#xD;
&#xD;
          -  Contraindication to jugular vein catheterization&#xD;
&#xD;
          -  Intracranial Hypertension&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hopital Europeen Marseille</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.</citation>
    <PMID>26903337</PMID>
  </results_reference>
  <results_reference>
    <citation>Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.</citation>
    <PMID>25693014</PMID>
  </results_reference>
  <results_reference>
    <citation>Allardet-Servent J, Castanier M, Signouret T, Soundaravelou R, Lepidi A, Seghboyan JM. Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study. Crit Care Med. 2015 Dec;43(12):2570-81. doi: 10.1097/CCM.0000000000001296.</citation>
    <PMID>26488219</PMID>
  </results_reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>March 10, 2018</last_update_submitted>
  <last_update_submitted_qc>March 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hôpital Européen Marseille</investigator_affiliation>
    <investigator_full_name>Jerome Allardet-Servent, MD</investigator_full_name>
    <investigator_title>MD, MSc</investigator_title>
  </responsible_party>
  <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>
  </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/NCT03004885
org study id: 2016-A01523-48
nct id: NCT03004885
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Acute Respiratory Distress Syndrome (ARDS) still remains associated with a mortality rate of
      30 - 45 % despite improvement in mechanical ventilation. Driving pressure, defined as the
      difference between the end-inspiratory and the end-expiratory airway pressure, appears as an
      important factor contributing to mortality in patients with the ARDS. In patients already
      receiving a conventional tidal volume of 6 ml/kg predicted body weight (PBW), a driving
      pressure ≥ 14 cmH2O increases the risk of death in the hospital. One mean to lower the
      driving pressure is to decrease the tidal volume such that from 6 to 4 ml/kg predicted body
      weight. However, this strategy promotes hypercarbia by reducing the alveolar ventilation,
      providing the respiratory rate is constant. In this setting, implementing an extracorporeal
      CO2 removal (ECCO2R) therapy may offset the associated hypercarbia. The investigators have
      previously demonstrated that combining a membrane oxygenator within an hemofiltration circuit
      provides efficacious low flow ECCO2R on a renal replacement therapy monitor. In this study,
      we thought to investigate the efficacy of the PrismaLung stand-alone therapy. Using a
      PrismaFlex monitor and a HP-X circuit, a neonatal membrane oxygenator (PrismaLung) is used to
      provide decarboxylation without renal replacement therapy. The study will consist in three
      periods:

        -  The first period will address the efficacy of the PrismaLung device at tidal volume of 6
           and 4 ml/kg PBW using an off-on-off design.

        -  The second part of the study will investigate the effect of varying the sweep gas flow
           and the mixture of the sweep gas on the CO2 removal rate (random order).

        -  The third part will compare three ventilatory strategies applied in a cross-over design
           :

             1. Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure
                (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).

             2. Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure
                between 23 - 25 cmH2O.

             3. Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table
                (ARMA).

      Each strategies will be apply in a random order for a duration of 22 hours. Pulmonary
      inflammatory and fibrosis pathway will be assess before and after each period using
      bronchoalveolar lavage (BAL) samples. Systemic inflammatory cytokines will also be
      investigate. Main measurements will include respiratory mechanics, transpulmonary pressure,
      work of breathing, end-expiratory lung volume and tidal ventilation using electrical
      impedance tomography.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change in PaCO2
time frame: 15 min after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW (during the first part of the study).
description: 20 % decrease in PaCO2 after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW versus 4 ml/kg PBW without ECCO2R.
measure: PaCO2
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Arterial blood gas
measure: CO2 removal rate
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Using both the blood side and the gas side equation
measure: Respiratory mechanics work of breathing
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)
measure: Transpulmonary pressure
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)
measure: Work of breathing
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)
measure: EIT
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Electrical Impedance Tomography using BB² (Swisstom)
measure: EELV
time frame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: End expiratory Lung volume using nitrogen wash-in wash-out method (Engstrom GE)
measure: Plasma Cytokines
time frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Elisa using plasma samples
measure: Pulmonary Cytokines
time frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: Elisa using BAL samples
measure: Pulmonary Type III Procollagen
time frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: RIA using plasma and BAL samples
measure: Pulmonary Inflammatory and Fibrotic pathway
time frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
description: mRNA
measure: Plasma Free Hemoglobin
time frame: q24 h, up to 72 h
measure: Haptoglobin
time frame: q24 h, up to 72 h
measure: Lacticodéshydrogenase (LDH)
time frame: q24 h, up to 72 h
measure: schizocytes
time frame: q24 h, up to 72 h
measure: Bilirubin
time frame: q24 h, up to 72 h
arm group label: Minimal Distension
arm group type: Experimental
description: Tidal volume 4 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R
arm group label: Maximal Recruitment
arm group type: Experimental
description: Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain plateau pressure between 23 - 25 cmH2O + ECCO2R
arm group label: Standard
arm group type: Active Comparator
description: Tidal volume 6 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R
intervention type: Device
intervention name: PrismaLung
description: Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator
arm group label: Maximal Recruitment
arm group label: Minimal Distension
arm group label: Standard
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
citation: Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
PMID: 26903337
citation: Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.
PMID: 25693014
citation: Allardet-Servent J, Castanier M, Signouret T, Soundaravelou R, Lepidi A, Seghboyan JM. Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study. Crit Care Med. 2015 Dec;43(12):2570-81. doi: 10.1097/CCM.0000000000001296.
PMID: 26488219
responsible party type: Principal Investigator
investigator affiliation: Hôpital Européen Marseille
investigator full name: Jerome Allardet-Servent, MD
investigator title: MD, MSc
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
sharing ipd: No