Project summary

Background Evidence for benefit of positive end–expiratory pressures (PEEP) in intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) under invasive mechanical ventilation is largely lacking. Nevertheless, higher PEEP is increasingly used in these patients.

Study design The trial of ‘REstricted versus Liberal positive end–expiratory pressures in patients without Acute respiratory distress syndrome’ (RELAx) is a national multicenter, non–inferiority, randomized controlled trial in adult ICU patients without ARDS but with an anticipated need for invasive mechanical ventilation lasting 24 hours or longer. RELAx will run in 12 ICUs in the Netherlands and will recruit 980 patients under invasive mechanical ventilation who will be randomly assigned to a restricted strategy using lowest possible PEEP starting at 5 cm H₂O (‘low PEEP’) versus a liberal strategy using PEEP at 8 cm H₂O (‘high PEEP’). The primary endpoint is the number of ‘ventilator–free days and alive at day 28’, a composite endpoint of ventilator dependency and mortality. Secondary endpoints include ICU– and hospital length of stay (LOS), ICU–, hospital –, and 90–day mortality, occurrence of severe hypoxemia, severe atelectasis, the need for rescue therapies, pulmonary complications, including pneumonia, pneumothorax, and development of ARDS. Hemodynamic support and sedation needs, the ‘Therapeutic Intervention Scoring System/Nursing Activities Score’ and related healthcare costs will also be compared between patients in the ‘low PEEP’ and patients in the ‘high PEEP’ arm of the trial.

Discussion RELAx is the first randomized controlled trial comparing low PEEP with high PEEP in ICU patients without ARDS at start of invasive mechanical ventilation that recruits a sufficient number of subjects to test the hypothesis that low PEEP PEEP is non–inferior to high PEEP with regard to a clinically relevant and objective outcome.

Trial registration ClinicalTrials.gov, NCT03167580 (May 23, 2017).