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

Phase 3

Recruiting

• Conditions: Extracorporeal Membrane Oxygenation Complication; Acute Respiratory Distress Syndrome

• Registration Number: NCT06814340
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-22
• Study First Submitted QC: 2025-02-03
• Study First Posted: 2025-02-07
• Status Verified: 2025-04
• Study Start: 2025-04
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-10
• Primary Completion: 2029-04
• Study Completion: 2030-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 280

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. 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 or being in the exclusion period at the end of a previous study, expect DRESSING-ECMO trial, which evaluates the use of sterile adhesive transparent dressings impregnated with Chlorhexidine gluconate on the cumulative incidence of ECMO cannula-related infection episodes.
14. Individuals under guardianship, or permanently legally incompetent adults

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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	Day 0 to Day 60	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.

Secondary Outcome Measures

Name	Time	Method
Hospital length of stay	From Day 1 to Day 90	Defined as total duration spent at the hospital between inclusion and D90
ECMO free days	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on ECMO-free days is defined as number of ECMO free-days between inclusion and D90
Invasive mechanical ventilation free days	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on invasive mecanical ventilation-free days between inclusion and D90
Renal replacement therapy-free days	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on renal function is defined as renal replacement therapy-free days between inclusion and D90
Continuous neuromuscular blockade-free days	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on continuous neuromuscular blockade is defined as number of continuous neuromuscular blockade-free days between inclusion and D90
Intervention side effects (ventilation-associated pneumonia)	From Day 1 to Day D14	Defined as the incidence of ventilation-associated pneumonia between inclusion and D14
Intervention side effets (need for inotropes or vasopressors)	From Day 1 to Day 14	Defined as the incidence of need for inotropes or vasopressors within 14 days on ECMO
Intervention side effets (intravenous sedation consumption)	From Day 1 to Day 14	Defined as the incidence of intravenous sedation consumption during the first 14 days on ECMO
Acute cor pulmonale	From Day 1 to Day 90	Defined as the incidence of acute cor pulmonale between inclusion and D90
Pneumothorax	From Day 1 to Day 90	Defined as the incidence of pneumothorax between inclusion and D90
Severe refractory hypoxemia on ECMO	From Day 1 to Day 90	Defined as the incidence of refractory severe hypoxemia between inclusion and D90
Compliance of the respiratory system at D7	From Day 1 to Day 7	Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D7
Compliance of the respiratory system at D10	From Day 1 to Day 10	Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D10
Compliance of the respiratory system at D14	From Day 1 to Day 14	Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D14
Compliance of the respiratory system at D28	From Day 1 to Day 28	Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D28
Right ventricular function at D7	From Day 1 to Day 7	Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D7 on ECMO following randomization
Right ventricular function at D14	From Day 1 to Day 14	Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D14 on ECMO following randomization
Right ventricular function at D28	From Day 1 to Day 28	Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D28 on ECMO following randomization
Duration of ECMO support	From Day 1 to Day 90	Defined as total duration with ECMO support between inclusion and D90
Mortality	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on mortality is defined as overall survival between inclusion and D90
Duration of invasive mechanical ventilation	From Day 1 to Day 90	Defined as total duration of invasive mechanical ventilation between inclusion and D90
Duration of Intensive Care Unit	From Day 1 to Day 90	Defined as total duration spent in intensive care unit between inclusion and D90
Need for lung transplant	From Day 1 to Day 90	Efficacy of early apneic ventilation during VV-ECMO on the need for a lung transplant is defined as lung transplant between inclusion and D90
Compliance of the respiratory system at D60	From Day 1 to Day 60	Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D60
Right ventricular function at D3	From Day 1 to Day 3	Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D3 on ECMO following randomization
Right ventricular function at D60	From Day 1 to Day 60	Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D60 on ECMO following randomization

Trial Locations

Locations (1)

Pitié-Salpêtrière Hospital; 🇫🇷 Paris, France