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NCT Number: NCT06814340

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

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.

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Key information

Conditions

Acute Respiratory Distress Syndrome Extracorporeal Membrane Oxygenation Complication Lung Diseases Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Avicenne Hospital, Bobigny, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Severe acute respiratory distress syndrome refractory to conventional therapy placed on VV-ECMO support in the 48 hours (maximum tolerance : +2h) preceding inclusion.
  • 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.
  • French Social security registration (except AME)

Exclusion criteria

  • Age < 18
  • Pregnancy or breastfeeding
  • Initiation of VV-ECMO > 48 h (maximum tolerance : +2h)
  • Cardiac arrest with cumulated no flow time &amp;gt;10 minutes before ECMO (within 48 hours prior to inclusion)
  • 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
  • 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
  • Individuals under guardianship, or permanently legally incompetent adults

Treatment and study plan

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.

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.

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

    Time frame: 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 outcomes

  1. Mortality

    Time frame: From Day 1 to Day 60

    Efficacy of early apneic ventilation during VV-ECMO on mortality is defined as overall survival between inclusion and D60

  2. Mortality

    Time frame: 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

  3. Need for lung transplant

    Time frame: From Day 1 to Day 60

    Efficacy of early apneic ventilation during VV-ECMO on the need for lung transplant is defined as lung transplant between inclusion and D60

  4. Need for lung transplant

    Time frame: 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

  5. Duration of ECMO support

    Time frame: From Day 1 to Day 60

    Defined as total duration with ECMO support between inclusion and D60

  6. Duration of ECMO support

    Time frame: From Day 1 to Day 90

    Defined as total duration with ECMO support between inclusion and D90

  7. Duration of invasive mechanical ventilation

    Time frame: From Day 1 to Day 60

    Defined as total duration of invasive mechanical ventilation between inclusion and D60

  8. Duration of invasive mechanical ventilation

    Time frame: From Day 1 to Day 90

    Defined as total duration of invasive mechanical ventilation between inclusion and D90

  9. Duration of Intensive Care Unit

    Time frame: From Day 1 to Day 60

    Defined as total duration spent in intensive care unit between inclusion and D60

  10. Duration of Intensive Care Unit

    Time frame: From Day 1 to Day 90

    Defined as total duration spent in intensive care unit between inclusion and D90

  11. Hospital length of stay

    Time frame: From Day 1 to Day 60

    Defined as total duration spent at the hospital between inclusion and D60

  12. Hospital length of stay

    Time frame: From Day 1 to Day 90

    Defined as total duration spent at the hospital between inclusion and D90

  13. ECMO free days

    Time frame: From Day 1 to Day 60

    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

  14. ECMO free days

    Time frame: 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

  15. Invasive mechanical ventilation free days

    Time frame: From Day 1 to Day 60

    Efficacy of early apneic ventilation during VV-ECMO on invasive mecanical ventilation-free days between inclusion and D60

  16. Invasive mechanical ventilation free days

    Time frame: From Day 1 to Day 90

    Efficacy of early apneic ventilation during VV-ECMO on invasive mecanical ventilation-free days between inclusion and D90

  17. Renal replacement therapy-free days

    Time frame: From Day 1 to Day 60

    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

  18. Renal replacement therapy-free days

    Time frame: 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

  19. Continuous neuromuscular blockade-free days

    Time frame: From Day 1 to Day 60

    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

  20. Continuous neuromuscular blockade-free days

    Time frame: 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

  21. Intervention side effects (ventilation-associated pneumonia)

    Time frame: From Day 1 to Day D14

    Defined as the incidence of ventilation-associated pneumonia between inclusion and D14

  22. Intervention side effets (need for inotropes or vasopressors)

    Time frame: From Day 1 to Day 14

    Defined as the incidence of need for inotropes or vasopressors within 14 days on ECMO

  23. Intervention side effets (intravenous sedation consumption)

    Time frame: From Day 1 to Day 14

    Defined as the incidence of intravenous sedation consumption during the first 14 days on ECMO

  24. Acute cor pulmonale

    Time frame: From Day 1 to Day 60

    Defined as the incidence of acute cor pulmonale between inclusion and D60

  25. Acute cor pulmonale

    Time frame: From Day 1 to Day 90

    Defined as the incidence of acute cor pulmonale between inclusion and D90

  26. Pneumothorax

    Time frame: From Day 1 to Day 60

    Defined as the incidence of pneumothorax between inclusion and D60

  27. Pneumothorax

    Time frame: From Day 1 to Day 90

    Defined as the incidence of pneumothorax between inclusion and D90

  28. Severe refractory hypoxemia on ECMO

    Time frame: From Day 1 to Day 60

    Defined as the incidence of refractory severe hypoxemia between inclusion and D60

  29. Severe refractory hypoxemia on ECMO

    Time frame: From Day 1 to Day 90

    Defined as the incidence of refractory severe hypoxemia between inclusion and D90

  30. Compliance of the respiratory system at D7

    Time frame: 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

  31. Compliance of the respiratory system at D10

    Time frame: 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

  32. Compliance of the respiratory system at D14

    Time frame: 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

  33. Compliance of the respiratory system at D28

    Time frame: 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

  34. Compliance of the respiratory system at D60

    Time frame: 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

  35. Right ventricular function at D3

    Time frame: 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

  36. Right ventricular function at D7

    Time frame: 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

  37. Right ventricular function at D14

    Time frame: 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

  38. Right ventricular function at D28

    Time frame: 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

  39. Right ventricular function at D60

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Matthieu SCHMIDT, MD

CONTACT

[email protected]

01 42 16 29 37

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: CALMDOWN

Important dates

Study start
2025
Primary completion
2029
Study completion
2030
First posted
Feb 7, 2025
Registry last updated
Apr 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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