"Continuous Positive Airway Pressure on Venovenous extracorporeaL Membrane Oxygenation for Acute respIratory Distress syndrOme"

NCT06814340 | Recruiting Phase 3

• 1 other identifier: APHP230850
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 11

Brief Summary

The CALMDOWN trial is a prospective, open-label, multicenter, comparative, controlled trial randomizing patients who received near apneic ventilation vs usual care on ECMO (ultra-protective lung ventilation). The study goal is to investigate the benefit of early apneic ventilation in the most severe forms of acute respiratory distress syndrome (ARDS) rescued by ECMO. Indeed, our hypothesis is that that early (near) apneic ventilation on venovenous ECMO for severe ARDS can enhance ventilator injury prevention and therefore reduce ECMO duration and mortality at Day 60.

Conditions

Extracorporeal Membrane Oxygenation Complication; Acute Respiratory Distress Syndrome

Keywords

ECMO; ARDS; CPAP

Outcome Measures

Primary Outcomes (1)

• Efficacy of the application of early apneic ventilation on four components : mortality status at D60, need for lung transplantation at D60, persisting ECMO at D60, number of days alive between randomization and day 60 without ECMO

  These components will be summarized in a composite, hierarchical outcome. Each patient will be 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 without lung transplantation or ECMO still ongoing at day 60 and the other did not, scores of +1 and -1 will be assigned, respectively. If both patients in the pairwise comparison survived without lung transplant or ECMO still ongoing at day 60, the assigned score will depend on which patient had more days free from ECMO: the patient with more days off ECMO 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 ECMO, or if both patients died or had a lung transplant, they will be both assigned a score of 0 for that pairwise comparison.

  Day 0 to Day 60

Secondary Outcomes (39)

• Mortality

  From Day 1 to Day 60

• Mortality

  From Day 1 to Day 90

• Need for lung transplant

  From Day 1 to Day 60

• Need for lung transplant

  From Day 1 to Day 90

• Duration of ECMO support

  From Day 1 to Day 60

Study Arms (2)

Intervention group : near apneic ventilation

EXPERIMENTAL

Patients will received near apneic ventilation during the first 3 days of ECMO.

Device: ECMO + near apneic ventilation

Standard of care : ultra-protective lung ventilation

ACTIVE COMPARATOR

Patients will receive ultra-protective lung ventilation as it uses on usual care on ECMO.

Device: ECMO + ultra-protective lung ventilation

Interventions

ECMO + near apneic ventilation DEVICE

Near apneic ventilation will be use during the first 3 days of ECMO. Patients will be ventilated in BIPAP/APRV or pressure-controlled ventilation. PEEP will be set to maintain the same mean airway pressure obtained during the standardized ventilation period pre-randomization to prevent lung derecruitment (PEEP ≥15cmH2O). If BIPAP/APRV is used, an RR of 2-4/min will be set with high pressure set at 30cmH20 for 3 sec. If pressure-controlled ventilation is selected, a respiratory rate of two sigh breaths/min with 30 cmH2O plateau pressure will be applied. Each sigh breath will be of three seconds duration. Neuromuscular blockade and sedation could be used at the discretion of the attending physician. After 3 days on ECMO, apneic ventilation could be pursued (at the physician's discretion). If not, ultra-protective lung ventilation will be applied (i.e standard of care). Prone positioning on ECMO will be left to the physicians' discretion.

Intervention group : near apneic ventilation

ECMO + ultra-protective lung ventilation DEVICE

Ultra-protective lung ventilation will be used up to the ECMO weaning. This group will receive ultra-protective lung ventilation with BIPAP/APRV or VCV mode setting a PEEP \>10 cmH2O, ΔP 14-15 cmH2O, RR 15-20/min, Vt 3-4ml/kg and lowest FiO2 to maintain SpO2\>92%. The use of prone positioning during ECMO will be left at the physician's discretion.

Standard of care : ultra-protective lung ventilation

Eligibility Criteria

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

You may qualify if:

• French Social security registration (except AME)

You may not qualify if:

• Age \< 18
• Pregnancy or breastfeeding
• Initiation of VV-ECMO \> 48 h (maximum tolerance : +2h)
• Irreversible neurological pathology
• End-stage chronic lung disease
• Contraindications for high PEEP level: untreated pneumothorax, barotrauma
• Irreversible ARDS with no hope for lung function recovery
• Patient moribund on the day of randomization, SAPS II \&amp;gt;90
• Liver cirrhosis (Child B or C)
• Lung transplantation
• Burns on more than 20 % of the body surface
• Individuals under guardianship, or permanently legally incompetent adults

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (11)

Avicenne Hospital

Bobigny, France

RECRUITING

Haut Levèque Hospital - CHU Bordeaux

Bordeaux, France

RECRUITING

Henri Mondor Hospital

Créteil, France

RECRUITING

Croix-Rousse Hospital - HCL

Lyon, France

RECRUITING

North Hospital - APHM

Marseille, France

RECRUITING

Mercy Hospital - CHR Metz

Metz, France

RECRUITING

Brabois Hospital - CHRU Nancy

Nancy, France

RECRUITING

CHU Orléans

Orléans, France

RECRUITING

Pitié-Salpêtrière Hospital

Paris, France

RECRUITING

Pontchaillou Hospital - CHU Rennes

Rennes, France

RECRUITING

CHU Tours

Tours, France

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Extracorporeal Membrane Oxygenation

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Respiratory Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

Matthieu SCHMIDT, MD

CONTACT

01 42 16 29 37; matthieu.schmidt@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 7, 2025
• Study Start: May 6, 2025
• Primary Completion (Estimated): May 6, 2029
• Study Completion (Estimated): May 6, 2030
• Last Updated: April 13, 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.

Locations

FR (11)