Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Intubation and Invasive mechanical ventilation ≤ 7 days

80 ≤ 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

Disqualifiers

Age <18 years

Pregnancy or breastfeeding

Catheter access to femoral vein or jugular vein impossible

Expected duration of mechanical ventilation < 48 hours

Trial design

Design model

Parallel

Treatments tested in this trial

  • ECLS

    Procedure/Surgery

    * 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

Treatment groups

290 Participants
are divided into 2 treatment groups
Group A: Expérimental : ECLSExperimental treatment 1 intervention
Group B: Control : Conventional Treatment ArmNo intervention 0 interventions

Trial outcomes

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.

Time frame
Day 30

Secondary outcomes

1

Mortality

Time frame
Day 30, Day 60, Day 90
2

Duration of mechanical ventilation

Time frame
From inclusion to Day 30, from inclusion to Day 60
3

Number of mechanical ventilation free days

Time frame
Day 30, Day 60
4

Duration of catecholamine hemodynamic support

Time frame
From inclusion to Day 30, from inclusion to Day 60

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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