Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS

NCT07516665 | Not Yet Recruiting

• 2 other identifiers: APHP240924IDRCB number
• Study Type: interventional
• Target: 290
• Locations: 0 countries
• Sites: N/A

Brief Summary

Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to \<6 ml/kg in order to achieve plateau pressures \<23-25 cm H₂O, driving pressures \<9-11 cm H₂O, and RR \<15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ \<120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Keywords

ECLS; Acute Respiratory Distress Syndorme (ARDS)

Outcome Measures

Primary Outcomes (1)

• Hierarchical criterion assessed at day 30, including all-cause mortality followed by the number of days free from MV at day 30, and calculated in such a manner that death constitutes a worse outcome than duration of ventilation.

  Each patient is compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better. \- If one patient survived at day 30 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 30, the assigned score will depend on which patient had more days free from MV at day 30: the patient with more days off MV will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of days off MV, or if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score.

  Day 30

Secondary Outcomes (27)

• Mortality

  Day 30, Day 60, Day 90

• Duration of mechanical ventilation

  From inclusion to Day 30, from inclusion to Day 60

• Number of mechanical ventilation free days

  Day 30, Day 60

• Duration of catecholamine hemodynamic support

  From inclusion to Day 30, from inclusion to Day 60

• Number of catecholamine hemodynamic support free days

  Day 30, Day 60

Study Arms (2)

Expérimental : ECLS

EXPERIMENTAL

* ECLS catheter s inserted, and EC LS initiated no later than 12h after randomization * Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9-11 cm H2O and at least 5 cm H 2 O ΔP decrease * PEEP adjusted to keep the same mean airway pressure * Pump outflow set at 2-4 L/min , based on the need of blood oxygenation * RR decreased to a min of 12/min with gas flow rate adjusted to maintain PaCO2 45 mmHg. * Protocolized weaning of ECLS

Procedure: ECLS

Control : Conventional Treatment Arm

NO INTERVENTION

* Conventional management of ARDS * Ventilatory settings: * Volume assist control mode, * VT 6 ml/kg of predicted body weight * PEEP adjusted for Pplateau 28 29 cmH2O ; * FiO2 for 88%≤SaO2≤95% or 55 mmHg≤PaO2≤80 mm Hg * RR up to 35/mn, for a PaCO2 resulting in 7.30\<pH\<7.42

Interventions

ECLS PROCEDURE

* ECLS catheters inserted, and EC LS initiated no later than 12h after randomization * Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9 -11 cmH2O and at least 5 cm H2O ΔP decrease * PEEP adjusted to keep the same mean airway pressure * Pump outflow set at 2-4 L/min , based on the need of blood oxygenation * RR decreased to a min of 12/min with gas flowrate adjusted to maintain PaCO2 45 mmHg. * Protocolized weaning of ECLS

Expérimental : ECLS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Intubation and Invasive mechanical ventilation ≤ 7 days
• Presence of all of the following conditions for ≤48 hours:
• ≤ PaO2/FiO2 ≤300 with PEEP \>5 cmH2O
• Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules
• Respiratory failure not fully explained by cardiac failure or fluid overload
• One of the following criteria (with Vt set at 6 mL/kg PBW):
• DeltaP ≥15 cm H2O OR
• Ventilatory ratio ≥2.2
• Social security registration (AME excluded)

You may not qualify if:

• Age \<18 years
• Pregnancy or breastfeeding
• Catheter access to femoral vein or jugular vein impossible
• Expected duration of mechanical ventilation \< 48 hours
• Chronic restrictive or obstructive (COPD) respiratory insufficiency with home ventilation or oxygen therapy
• Currently receiving ECLS therapy
• Severe cardiac failure or ongoing acute coronary syndrome
• Heparin-induced thrombocytopenia
• Severe underlying pre-existing condition with expected six-month mortality \>50%
• Contraindication for systemic anticoagulation (including platelet count \<50G/L)
• Patient moribund, decision to limit therapeutic interventions
• Acute brain injury or irreversible neurological pathology
• Bone marrow transplantation within the last 1 year
• Actual body weight exceeding 1 kg per centimeter of height
• Prior enrolment in the trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Central Study Contacts

Alain COMBES, Professor of medicine

CONTACT

+33142163818; alain.combes@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, prospective, randomized, comparative open trial

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 8, 2026
• Study Start: May 11, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal