"Continuous Positive Airway Pressure on Venovenous extracorporeaL Membrane Oxygenation for Acute respIratory Distress syndrOme" - CALMDOWN
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 280
- Locations
- 14
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •Pregnancy or breastfeeding
- •Initiation of VV-ECMO > 48 h (maximum tolerance : +2h)
- •Cardiac arrest with cumulated no flow time >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 >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
Arms & Interventions
Intervention group : near apneic ventilation
Patients will received near apneic ventilation during the first 3 days of ECMO.
Intervention: ECMO + near apneic ventilation (Device)
Standard of care : ultra-protective lung ventilation
Patients will receive ultra-protective lung ventilation as it uses on usual care on ECMO.
Intervention: ECMO + ultra-protective lung ventilation (Device)
Outcomes
Primary Outcomes
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
- Mortality(From Day 1 to Day 60)
- Need for lung transplant(From Day 1 to Day 60)
- Duration of ECMO support(From Day 1 to Day 60)
- Duration of invasive mechanical ventilation(From Day 1 to Day 60)
- Duration of Intensive Care Unit(From Day 1 to Day 60)
- Hospital length of stay(From Day 1 to Day 60)
- ECMO free days(From Day 1 to Day 60)
- Invasive mechanical ventilation free days(From Day 1 to Day 60)
- Renal replacement therapy-free days(From Day 1 to Day 60)
- Continuous neuromuscular blockade-free days(From Day 1 to Day 60)
- Acute cor pulmonale(From Day 1 to Day 60)
- Pneumothorax(From Day 1 to Day 60)
- Severe refractory hypoxemia on ECMO(From Day 1 to Day 60)
- Hospital length of stay(From Day 1 to Day 90)
- ECMO free days(From Day 1 to Day 90)
- Invasive mechanical ventilation free days(From Day 1 to Day 90)
- Renal replacement therapy-free days(From Day 1 to Day 90)
- Continuous neuromuscular blockade-free days(From Day 1 to Day 90)
- Intervention side effects (ventilation-associated pneumonia)(From Day 1 to Day D14)
- Intervention side effets (need for inotropes or vasopressors)(From Day 1 to Day 14)
- Intervention side effets (intravenous sedation consumption)(From Day 1 to Day 14)
- Acute cor pulmonale(From Day 1 to Day 90)
- Pneumothorax(From Day 1 to Day 90)
- Severe refractory hypoxemia on ECMO(From Day 1 to Day 90)
- Compliance of the respiratory system at D7(From Day 1 to Day 7)
- Compliance of the respiratory system at D10(From Day 1 to Day 10)
- Compliance of the respiratory system at D14(From Day 1 to Day 14)
- Compliance of the respiratory system at D28(From Day 1 to Day 28)
- Right ventricular function at D7(From Day 1 to Day 7)
- Right ventricular function at D14(From Day 1 to Day 14)
- Right ventricular function at D28(From Day 1 to Day 28)
- Duration of ECMO support(From Day 1 to Day 90)
- Mortality(From Day 1 to Day 90)
- Duration of invasive mechanical ventilation(From Day 1 to Day 90)
- Duration of Intensive Care Unit(From Day 1 to Day 90)
- Need for lung transplant(From Day 1 to Day 90)
- Compliance of the respiratory system at D60(From Day 1 to Day 60)
- Right ventricular function at D3(From Day 1 to Day 3)
- Right ventricular function at D60(From Day 1 to Day 60)