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RECRUITING
NCT06849570
NA

Assessment of the PEEP Responsiveness to Titrate End-expiratory Pressure and of the Need for Muscle Relaxation During Prone Positioning in Moderate-to-severe Acute Respiratory Distress Syndrome: A Master Protocol

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

Summary

Despite best supportive care, mortality of the Acute Respiratory Distress Syndrom (ARDS) remains high. In the absence of specific treatments, providing safe and efficient mechanical ventilation (MV) is key to survival. The use of low tidal volumes (VT) and plateau pressures (PPLAT) improves survival in randomized controlled trials (RCTs), but the safest VT to be applied for each patient remains unknown. Whether targeting low ∆P instead of a 6 mL/kg VT improves outcome has not been tested prospectively. The optimal method to set PEEP is also a matter of debate. As the amount of potentially recruitable lung vary widely among patients and is strongly associated with the response to PEEP, it may be necessary to tailor PEEP settings based on the response to a PEEP trial. The first aim is to test a personalized approach to set PEEP widely supported by the literature. The first hypothesis is that i) patients with greater amounts of recruitable lung may benefit from higher PEEP levels, provided that attention is paid to maintain ∆P below 14 cmH2O, ii) setting PEEP based on results of a PEEP-responsiveness test improves survival as compared to low- and high-PEEP strategies applied independently of the patient response. Apart from VT reduction and PPLAT control below 30 cmH2O, only 2 interventions demonstrated a reduction of mortality in large RCTs: a 48-hour continuous infusion of neuromuscular blocking agents (NMBAs) at the acute phase of ARDS6 and the use of prone positioning (PP). Whereas there is little doubt on the utility of PP in patients with PaO2/FiO2 ratio \< 150 mmHg, there is more controversy on the impact of NMBAs on survival. Despite a strong rationale and a very widespread use in clinical practice, no current guidelines answer the question of the best timing of muscle relaxation in moderate to severe ARDS patients treated with PP. As a second aim, the hypothesis is that the early systematic and combined use of NMBAs improved survival of patients with moderate to severe ARDS requiring prone positioning after optimization of PEEP settings.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

1200

Start Date

2025-11-05

Completion Date

2029-11-05

Last Updated

2026-08-28

Healthy Volunteers

No

Interventions

OTHER

Minimal distension

Patients receive tidal volume (VT) of 6 mL/kg and conservative positive end-expiratory pressure (PEEP) setting.

OTHER

Maximal Recruitment

Patients receive tidal volume adjusted to limit plateau pressure (∆P) to 14 cmH2O and the highest possible PEEP while maintaining plateau pressure (PPLAT) ≤ 27 cmH2O.

OTHER

Prone position + early NMBAs

NMBAs given as soon as possible after randomization

OTHER

Prone position + rescue NMBAs

NMBAs given only as a rescue

Locations (29)

CH Aix

Aix-en-Provence, France

Hôpital Pellegrin

Bordeaux, France

CH Fleyriat

Bourg-en-Bresse, France

Cavale Blanche

Brest, France

CHU de Caen Normandie

Caen, France

Hôpital de Dieppe

Dieppe, France

CHI Fréjus Saint Raphaël

Fréjus, France

Hôpital Raymond Poincaré AP-HP

Garches, France

CHU Grenoble

Grenoble, France

CH de Bicêtre

Le Kremlin-Bicêtre, France

CH du Mans

Le Mans, France

Croix Rousse

Lyon, France

Groupement Hospitalier Sud

Lyon, France

Hôpital Sait Joseph Saint Luc

Lyon, France

APHM CHU Nord

Marseille, France

La Timone

Marseille, France

Hôpital de Brabois

Nancy, France

CHU de Nantes

Nantes, France

Hopital de l'Archet 1

Nice, France

Hôpital Cochin AP-HP

Paris, France

Hôpital de La Pitié Salpetrière AP-HP

Paris, France

Hôpital Saint Louis

Paris, France

La Pitié Salpetriere hospital - AP-HP

Paris, France

Hôpital Charles Nicolle

Rouen, France

Hôpital Nord

Saint-Etienne, France

CMC Foch

Suresnes, France

Hôpital Bretonneau

Tours, France

Centre Hospitalier de Troyes

Troyes, France

Hôpital André Mignot

Versailles, France