Clinical trial NCT06814340: "Continuous Positive Airway Pressure on Venovenous extracorporeaL Membrane Oxygenation for Acute respIratory Distress syndrOme"
Official title: "Continuous Positive Airway Pressure on Venovenous extracorporeaL Membrane Oxygenation for Acute respIratory Distress syndrOme" - CALMDOWN
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Extracorporeal Membrane Oxygenation Complication
Keywords: ECMO
ARDS
CPAP
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-02-07
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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. 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

Primary outcomes:
measure: 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
timeFrame: Day 0 to Day 60
Secondary outcomes:
measure: Mortality
timeFrame: From Day 1 to Day 60
measure: Mortality
timeFrame: From Day 1 to Day 90
measure: Need for lung transplant
timeFrame: From Day 1 to Day 60
measure: Need for lung transplant
timeFrame: From Day 1 to Day 90
measure: Duration of ECMO support
timeFrame: From Day 1 to Day 60
measure: Duration of ECMO support
timeFrame: From Day 1 to Day 90
measure: Duration of invasive mechanical ventilation
timeFrame: From Day 1 to Day 60
measure: Duration of invasive mechanical ventilation
timeFrame: From Day 1 to Day 90
measure: Duration of Intensive Care Unit
timeFrame: From Day 1 to Day 60
measure: Duration of Intensive Care Unit
timeFrame: From Day 1 to Day 90
measure: Hospital length of stay
timeFrame: From Day 1 to Day 60
measure: Hospital length of stay
timeFrame: From Day 1 to Day 90
measure: ECMO free days
timeFrame: From Day 1 to Day 60
measure: ECMO free days
timeFrame: From Day 1 to Day 90
measure: Invasive mechanical ventilation free days
timeFrame: From Day 1 to Day 60
measure: Invasive mechanical ventilation free days
timeFrame: From Day 1 to Day 90
measure: Renal replacement therapy-free days
timeFrame: From Day 1 to Day 60
measure: Renal replacement therapy-free days
timeFrame: From Day 1 to Day 90
measure: Continuous neuromuscular blockade-free days
timeFrame: From Day 1 to Day 60
measure: Continuous neuromuscular blockade-free days
timeFrame: From Day 1 to Day 90
measure: Intervention side effects (ventilation-associated pneumonia)
timeFrame: From Day 1 to Day D14
measure: Intervention side effets (need for inotropes or vasopressors)
timeFrame: From Day 1 to Day 14
measure: Intervention side effets (intravenous sedation consumption)
timeFrame: From Day 1 to Day 14
measure: Acute cor pulmonale
timeFrame: From Day 1 to Day 60
measure: Acute cor pulmonale
timeFrame: From Day 1 to Day 90
measure: Pneumothorax
timeFrame: From Day 1 to Day 60
measure: Pneumothorax
timeFrame: From Day 1 to Day 90
measure: Severe refractory hypoxemia on ECMO
timeFrame: From Day 1 to Day 60
measure: Severe refractory hypoxemia on ECMO
timeFrame: From Day 1 to Day 90
measure: Compliance of the respiratory system at D7
timeFrame: From Day 1 to Day 7
measure: Compliance of the respiratory system at D10
timeFrame: From Day 1 to Day 10
measure: Compliance of the respiratory system at D14
timeFrame: From Day 1 to Day 14
measure: Compliance of the respiratory system at D28
timeFrame: From Day 1 to Day 28
measure: Compliance of the respiratory system at D60
timeFrame: From Day 1 to Day 60
measure: Right ventricular function at D3
timeFrame: From Day 1 to Day 3
measure: Right ventricular function at D7
timeFrame: From Day 1 to Day 7
measure: Right ventricular function at D14
timeFrame: From Day 1 to Day 14
measure: Right ventricular function at D28
timeFrame: From Day 1 to Day 28
measure: Right ventricular function at D60
timeFrame: From Day 1 to Day 60
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
Study officials:
References: