A Phase 3 interventional study of ECMO + near apneic ventilation and ECMO + ultra-protective lung ventilation in Acute Respiratory Distress Syndrome and Extracorporeal Membrane Oxygenation Complication, sponsored by Assistance Publique - Hôpitaux de Paris. Recruiting at 11 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
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.
1,597 studies on the registry are indexed under Respiratory Distress Syndrome; 312 are open to participants now.
This study's planned enrollment of 280 is above the median of 60 across 961 interventional studies indexed under Respiratory Distress Syndrome.
Browse Respiratory Distress Syndrome studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients will received near apneic ventilation during the first 3 days of ECMO.
Device: ECMO + near apneic ventilation
Patients will receive ultra-protective lung ventilation as it uses on usual care on ECMO.
Device: ECMO + ultra-protective lung ventilation
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.
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.
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.
Time frame: Day 0 to Day 60
Mortality
Efficacy of early apneic ventilation during VV-ECMO on mortality is defined as overall survival between inclusion and D60
Time frame: From Day 1 to Day 60
Mortality
Efficacy of early apneic ventilation during VV-ECMO on mortality is defined as overall survival between inclusion and D90
Time frame: From Day 1 to Day 90
Need for lung transplant
Efficacy of early apneic ventilation during VV-ECMO on the need for lung transplant is defined as lung transplant between inclusion and D60
Time frame: From Day 1 to Day 60
Need for lung transplant
Efficacy of early apneic ventilation during VV-ECMO on the need for a lung transplant is defined as lung transplant between inclusion and D90
Time frame: From Day 1 to Day 90
Duration of ECMO support
Defined as total duration with ECMO support between inclusion and D60
Time frame: From Day 1 to Day 60
Duration of ECMO support
Defined as total duration with ECMO support between inclusion and D90
Time frame: From Day 1 to Day 90
Duration of invasive mechanical ventilation
Defined as total duration of invasive mechanical ventilation between inclusion and D60
Time frame: From Day 1 to Day 60
Duration of invasive mechanical ventilation
Defined as total duration of invasive mechanical ventilation between inclusion and D90
Time frame: From Day 1 to Day 90
Duration of Intensive Care Unit
Defined as total duration spent in intensive care unit between inclusion and D60
Time frame: From Day 1 to Day 60
Duration of Intensive Care Unit
Defined as total duration spent in intensive care unit between inclusion and D90
Time frame: From Day 1 to Day 90
Hospital length of stay
Defined as total duration spent at the hospital between inclusion and D60
Time frame: From Day 1 to Day 60
Hospital length of stay
Defined as total duration spent at the hospital between inclusion and D90
Time frame: From Day 1 to Day 90
ECMO free days
Efficacy of early apneic ventilation during VV-ECMO on ECMO-free days is defined as the number of ECMO free-days between inclusion and D60
Time frame: From Day 1 to Day 60
ECMO free days
Efficacy of early apneic ventilation during VV-ECMO on ECMO-free days is defined as number of ECMO free-days between inclusion and D90
Time frame: From Day 1 to Day 90
Invasive mechanical ventilation free days
Efficacy of early apneic ventilation during VV-ECMO on invasive mecanical ventilation-free days between inclusion and D60
Time frame: From Day 1 to Day 60
Invasive mechanical ventilation free days
Efficacy of early apneic ventilation during VV-ECMO on invasive mecanical ventilation-free days between inclusion and D90
Time frame: From Day 1 to Day 90
Renal replacement therapy-free days
Efficacy of early apneic ventilation during VV-ECMO on renal function is defined as number of renal replacement therapy-free days between inclusion and D60
Time frame: From Day 1 to Day 60
Renal replacement therapy-free days
Efficacy of early apneic ventilation during VV-ECMO on renal function is defined as renal replacement therapy-free days between inclusion and D90
Time frame: From Day 1 to Day 90
Continuous neuromuscular blockade-free days
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 D60
Time frame: From Day 1 to Day 60
Continuous neuromuscular blockade-free days
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
Time frame: From Day 1 to Day 90
Intervention side effects (ventilation-associated pneumonia)
Defined as the incidence of ventilation-associated pneumonia between inclusion and D14
Time frame: From Day 1 to Day D14
Intervention side effets (need for inotropes or vasopressors)
Defined as the incidence of need for inotropes or vasopressors within 14 days on ECMO
Time frame: From Day 1 to Day 14
Intervention side effets (intravenous sedation consumption)
Defined as the incidence of intravenous sedation consumption during the first 14 days on ECMO
Time frame: From Day 1 to Day 14
Acute cor pulmonale
Defined as the incidence of acute cor pulmonale between inclusion and D60
Time frame: From Day 1 to Day 60
Acute cor pulmonale
Defined as the incidence of acute cor pulmonale between inclusion and D90
Time frame: From Day 1 to Day 90
Pneumothorax
Defined as the incidence of pneumothorax between inclusion and D60
Time frame: From Day 1 to Day 60
Pneumothorax
Defined as the incidence of pneumothorax between inclusion and D90
Time frame: From Day 1 to Day 90
Severe refractory hypoxemia on ECMO
Defined as the incidence of refractory severe hypoxemia between inclusion and D60
Time frame: From Day 1 to Day 60
Severe refractory hypoxemia on ECMO
Defined as the incidence of refractory severe hypoxemia between inclusion and D90
Time frame: From Day 1 to Day 90
Compliance of the respiratory system at D7
Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D7
Time frame: From Day 1 to Day 7
Compliance of the respiratory system at D10
Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D10
Time frame: From Day 1 to Day 10
Compliance of the respiratory system at D14
Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D14
Time frame: From Day 1 to Day 14
Compliance of the respiratory system at D28
Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D28
Time frame: From Day 1 to Day 28
Compliance of the respiratory system at D60
Effect of near apneic ventilation on the improvement of the compliance of the respiratory system (ml/cmH2O) at D60
Time frame: From Day 1 to Day 60
Right ventricular function at D3
Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D3 on ECMO following randomization
Time frame: From Day 1 to Day 3
Right ventricular function at D7
Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D7 on ECMO following randomization
Time frame: From Day 1 to Day 7
Right ventricular function at D14
Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D14 on ECMO following randomization
Time frame: From Day 1 to Day 14
Right ventricular function at D28
Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D28 on ECMO following randomization
Time frame: From Day 1 to Day 28
Right ventricular function at D60
Effect of near apneic ventilation on right ventricular function evaluated by echocardiograohy (RV/LV diameter ratio) at D60 on ECMO following randomization
Time frame: From Day 1 to Day 60
Plan to share: Yes — The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Supporting information: Study protocol, Sap, Icf
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Respiratory Distress Syndrome→
Assistance Publique - Hôpitaux de Paris