Using near apneic ventilation with ECMO for severe respiratory distress

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

This study is testing if a new way of breathing support called near apneic ventilation can help patients with severe respiratory distress on ECMO recover better and faster than the usual care.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 280 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 11 sites (Bobigny and 10 other locations)
• Trial ID: NCT06814340 on ClinicalTrials.gov

What this trial studies

The CALMDOWN trial is a multicenter, open-label, controlled trial that aims to compare the effects of near apneic ventilation versus usual care in patients with severe acute respiratory distress syndrome (ARDS) who are on venovenous extracorporeal membrane oxygenation (VV-ECMO). The study hypothesizes that early implementation of near apneic ventilation can prevent ventilator-induced lung injury, potentially leading to reduced ECMO duration and lower mortality rates at Day 60. Patients will be randomized to receive either near apneic ventilation or ultra-protective lung ventilation while on ECMO support.

Who should consider this trial

Good fit: Ideal candidates are adults with severe ARDS who are refractory to conventional therapy and have been placed on VV-ECMO within 48 hours.

Not a fit: Patients under 18 years old, pregnant or breastfeeding women, and those who have been on VV-ECMO for more than 48 hours are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve outcomes for patients with severe ARDS by reducing mortality and the duration of ECMO support.

How similar studies have performed: While the approach of using near apneic ventilation in this context is novel, similar studies have shown promising results in improving outcomes for patients on ECMO.

Eligibility criteria

Inclusion Criteria:

1. Severe acute respiratory distress syndrome refractory to conventional therapy placed on VV-ECMO support in the 48 hours (maximum tolerance : +2h) preceding inclusion.
2. Obtain informed consent from a close relative or surrogate. According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patient is unable to give his/her consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow.
3. French Social security registration (except AME)

Exclusion Criteria:

1. Age \< 18
2. Pregnancy or breastfeeding
3. Initiation of VV-ECMO \> 48 h (maximum tolerance : +2h)
4. Cardiac arrest with cumulated no flow time \&amp;gt;10 minutes before ECMO (within 48 hours prior to inclusion)
5. Irreversible neurological pathology
6. End-stage chronic lung disease
7. Contraindications for high PEEP level: untreated pneumothorax, barotrauma
8. Irreversible ARDS with no hope for lung function recovery
9. Patient moribund on the day of randomization, SAPS II \&amp;gt;90
10. Liver cirrhosis (Child B or C)
11. Lung transplantation
12. Burns on more than 20 % of the body surface
13. Participation in another interventional study with a similar primary endpoint (mortality, lung transplantation, or duration of ECMO) or being in the exclusion period at the end of a previous study
14. Individuals under guardianship, or permanently legally incompetent adults

Where this trial is running

Bobigny and 10 other locations

• 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)

Study contacts

• Study coordinator: Matthieu SCHMIDT, MD

Conditions Acute Respiratory Distress Syndrome; Extracorporeal Membrane Oxygenation Complication; ECMO; ARDS; CPAP