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Enhanced Lung Protective Ventilation With ECCO2R During ARDS (PROVE)

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ClinicalTrials.gov Identifier: NCT03525691
Recruitment Status : Recruiting
First Posted : May 16, 2018
Last Update Posted : August 9, 2022
Sponsor:
Information provided by (Responsible Party):
Jerome Allardet-Servent, MD, Hôpital Européen Marseille

Tracking Information
First Submitted Date  ICMJE May 3, 2018
First Posted Date  ICMJE May 16, 2018
Last Update Posted Date August 9, 2022
Actual Study Start Date  ICMJE May 23, 2018
Estimated Primary Completion Date July 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
Change in PaCO2 [ Time Frame: 15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW. ]
20 % decrease in PaCO2 after initiation of ECCO2R at tidal volume of 4 ml/kg PBW (as compared to 4 ml/kg without ECCO2R)
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
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) ]
20 % decrease in PaCO2 after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW versus 4 ml/kg PBW without ECCO2R.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
  • PaCO2 [ Time Frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Arterial blood gas analyser (RAPIDPoint 500)
  • CO2 removal rate [ Time Frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using measurements from both the blood side and the gas side (two methods)
  • Transpulmonary pressure and work of breathing [ Time Frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using an oesophageal balloon catheter (NutriVent catheter) and a dedicated monitor (FluxMed, MBMed)
  • Regional tidal ventilation [ Time Frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using an Electrical Impedance Tomography device (BB², Swisstom)
  • End-expiratory Lung Volume [ Time Frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using the nitrogen wash-in wash-out method (Engstrom GE)
  • Plasma Cytokines [ Time Frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using Elisa custom kit (Qiagen) from plasma samples
  • Pulmonary Cytokines [ Time Frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using Elisa custom kit (Qiagen) from BAL samples
  • Type III Procollagen [ Time Frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using both RIA and Elisa methods from plasma and BAL samples
  • Pulmonary Inflammatory and Fibrotic pathway [ Time Frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm. ]
    Using mRNA custom kit RT-PCR analysis (Qiagen) from BAL samples
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • 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. ]
    Arterial blood gas analyser (RAPIDPoint 500)
  • CO2 removal rate [ Time Frame: 15 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 ]
    Using measurement methods from both the blood side and the gas side
  • Transpulmonary pressure and 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 ]
    Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)
  • Regional tidal ventilation [ 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 ]
    Using Electrical Impedance Tomography using BB² (Swisstom)
  • End-expiratory Lung Volume [ 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 ]
    Using the nitrogen wash-in wash-out method (Engstrom GE)
  • Plasma Cytokines [ Time Frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm ]
    Using Elisa custom kit (Qiagen) from plasma samples
  • Pulmonary Cytokines [ Time Frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm ]
    Using Elisa custom kit (Qiagen) from BAL samples
  • Type III Procollagen [ Time Frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm ]
    Using both RIA and Elisa methods from plasma and BAL samples
  • Pulmonary Inflammatory and Fibrotic pathway [ Time Frame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm ]
    Using mRNA custom kit RT-PCR analysis (Qiagen) from BAL samples
Current Other Pre-specified Outcome Measures
 (submitted: May 17, 2018)
  • Plasma Free Hemoglobin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples
  • Haptoglobin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples
  • Lacticodéshydrogenase (LDH) [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples
  • schizocytes [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples
  • Bilirubin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples
Original Other Pre-specified Outcome Measures
 (submitted: May 3, 2018)
  • Plasma Free Hemoglobin [ Time Frame: q24 h, up to 72 h ]
  • Haptoglobin [ Time Frame: q24 h, up to 72 h ]
  • Lacticodéshydrogenase (LDH) [ Time Frame: q24 h, up to 72 h ]
  • schizocytes [ Time Frame: q24 h, up to 72 h ]
  • Bilirubin [ Time Frame: q24 h, up to 72 h ]
 
Descriptive Information
Brief Title  ICMJE Enhanced Lung Protective Ventilation With ECCO2R During ARDS
Official Title  ICMJE Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome
Brief Summary

Acute Respiratory Distress Syndrome (ARDS) is associated with a mortality rate of 30 - 45 % and required invasive mechanical ventilation (MV) in almost 85 % of patients[1]. During controlled MV, driving pressure (i.e., the difference between end-inspiratory and end-expiratory airway pressure) depends of both tidal volume and respiratory system compliance. Either excessive tidal volume or reduced lung aeration may increase the driving pressure. ARDS patients receiving tidal volume of 6 ml/kg predicted body weight (PBW) and having a day-1 driving pressure ≥ 14 cmH2O have an increased risk of death in the hospital[2]. Seemly, in the LUNG SAFE observational cohort, ARDS patients having a day-1 driving pressure < 11 cmH2O had the lowest risk of death in the hospital[1]. Hence, driving pressure acts as a major contributor of mortality in ARDS, and probably reflects excessive regional lung distension resulting in pro-inflammatory and fibrotic biological processes. Whether decreasing the driving pressure by an intervention change mortality remains an hypothesis; but one of means is to decrease the tidal volume from 6 to 4 ml/ kg predicted body weight (PBW). However, this strategy promotes hypercarbia, at constant respiratory rate, by decreasing the alveolar ventilation. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy prevents from hypercarbia. A number of low-flow ECCO2R devices are now available and some of those use renal replacement therapy (RRT) platform. The investigators previously reported that combining a membrane oxygenator (0.65 m²) within a hemofiltration circuit provides efficacious low flow ECCO2R and blood purification in patients presenting with both ARDS and Acute Kidney injury[3].

This study aims to investigate the efficacy of an original ECCO2R system combining a 0.67 m² membrane oxygenator (Lilliput 2, SORIN) inserted within a specific circuit (HP-X, BAXTER) and mounted on a RRT monitor (PrismafleX, BAXTER). Such a therapy only aims to provide decarboxylation but not blood purification and has the huge advantage to be potentially implemented in most ICUs without requiring a specific ECCO2R device. The study will consist in three periods:

  • The first period will address the efficacy of this original ECCO2R system at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design.
  • The second part will investigate the effect of varying the sweep gas flow (0-2-4-6-8-10 l/min) and the mixture of the sweep gas (Air/O2) on the CO2 removal rate.
  • The third part will compare three ventilatory strategies applied in a crossover 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • ARDS, Human
  • Ventilator-Induced Lung Injury
Intervention  ICMJE Device: Low flow Extracorporeal CO2 removal
Low flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX)
Study Arms  ICMJE
  • Experimental: Minimal distension
    Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min)
    Intervention: Device: Low flow Extracorporeal CO2 removal
  • Experimental: Maximal recruitment
    Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min)
    Intervention: Device: Low flow Extracorporeal CO2 removal
  • Active Comparator: Standard
    Tidal volume 6 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R (no sweep gas flow, blood flow = 400 mL/min)
    Intervention: Device: Low flow Extracorporeal CO2 removal
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2018)
14
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 21, 2024
Estimated Primary Completion Date July 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ARDS moderate or severe (Berlin criteria)
  • Onset < 48 h
  • Driving pressure ≥ 11 cmH2O

Exclusion Criteria:

  • Lack of consent or social protection
  • Chronic respiratory failure (requiring Oxygen or NIPPV)
  • Severe hypoxemia: PaO2/FIO2 < 80 with PEEP ≥ 18 cmH2O AND FIO2= 1
  • Acute Renal Failure requiring RRT
  • DNR order or death expected within the next 72 hours
  • Planned surgery or transport out-of-ICU expected within the next 72 hours
  • Heparin allergy
  • Contraindication to jugular vein catheterization
  • Intracranial Hypertension
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jérôme ALLARDET-SERVENT, MD +33413427155 j.allardetservent@hopital-europeen.fr
Contact: Wahiba BIDAUT w.bidaut@hopital-europeen.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03525691
Other Study ID Numbers  ICMJE 2017-A03647-46
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Jerome Allardet-Servent, MD, Hôpital Européen Marseille
Original Responsible Party Jerome Allardet-Servent, MD, Hôpital Européen Marseille, MD, MSc
Current Study Sponsor  ICMJE Hôpital Européen Marseille
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jérôme ALLARDET-SERVENT, MD Hopital Européen Marseille
PRS Account Hôpital Européen Marseille
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP