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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

Study Description
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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).

Condition or disease Intervention/treatment Phase
ARDS, Human Ventilator-Induced Lung Injury Device: Low flow Extracorporeal CO2 removal Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome
Actual Study Start Date : May 23, 2018
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : December 21, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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)
 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)
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)
 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)
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)
 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)


Outcome Measures
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Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. 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

  9. 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


Other Outcome Measures:
  1. Plasma Free Hemoglobin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples

  2. Haptoglobin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples

  3. Lacticodéshydrogenase (LDH) [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples

  4. schizocytes [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples

  5. Bilirubin [ Time Frame: every 24 hours, up to 72 hours. ]
    serum samples


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525691


Contacts
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Contact: Jérôme ALLARDET-SERVENT, MD +33413427155 j.allardetservent@hopital-europeen.fr
Contact: Wahiba BIDAUT w.bidaut@hopital-europeen.fr

Locations
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France
Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE Recruiting
Marseille, France
Contact: Jérôme ALLARDET-SERVENT, MD, MSc    +33413427155    j.allardetservent@hopital-europeen.fr   
Principal Investigator: Jérôme ALLARDET-SERVENT, MD         
Sub-Investigator: Matthias CASTANIER, MD         
Sub-Investigator: Claire CAMUS, PhD         
Sponsors and Collaborators
Hôpital Européen Marseille
Investigators
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Principal Investigator: Jérôme ALLARDET-SERVENT, MD Hopital Européen Marseille
More Information
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Publications of Results:

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Responsible Party: Jerome Allardet-Servent, MD, Principal Investigator, Hôpital Européen Marseille
ClinicalTrials.gov Identifier: NCT03525691    
Other Study ID Numbers: 2017-A03647-46
First Posted: May 16, 2018    Key Record Dates
Last Update Posted: August 9, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Injury
Respiratory Distress Syndrome
Ventilator-Induced Lung Injury
Lung Diseases
 Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries
Respiration Disorders