Mercat 2008.

Study characteristics
Methods	Multi‐centre randomised controlled trial conducted in 37 ICUs in France Time period of study: September 2002 through December 2005
Participants	767 participants aged > 18 (37 centres) Included: ARDS Excluded: known pregnancy, participation in another trial within 30 days, increased intracranial pressure, sickle cell disease, severe chronic respiratory disease requiring oxygen therapy or home MV, actual body weight exceeding 1 kg/cm of height, severe burns, severe chronic liver disease, bone marrow transplant or chemotherapy‐induced neutropenia, pneumothorax, expected duration of MV ≤ 48 hours, decision to withhold life‐sustaining treatment Study authors estimated that a sample size of 400 patients per group would provide 80% power at a 2‐sided α level of.05 to detect a 10% absolute reduction in mortality. Interim analyses were designed to allow early termination of the trial
Interventions	Control (382) and intervention (385): MV ventilator mode (both groups): volume‐assist control, TV 6 mL/kg PBW, plateau pressure limit ≤ 30 cmH₂O, respiratory rate (breaths/min) ≤ 35 adjusted for pH between 7.30 and 7.45, recruiting manoeuvres: allowed but not recommended Target ranges for oxygenation: PaO₂ between 55 and 80 mmHg; SpO₂ between 88% and 95% PEEP Control: total PEEP between 5 and 9 cmH₂O, mean PEEP values on Days 1 through 3 of 6.9 cmH₂O Intervention: PEEP level to achieve plateau pressures between 28 and 30 cmH₂O, mean PEEP values on Days 1 through 3 of 14 cmH₂O Use of rescue therapies (both groups) when oxygenation goal was not met despite FIO₂ ≥ 0.8 and highest allowed total PEEP level in the relevant arm
Outcomes	Primary: mortality at Day 28 Secondary: mortality at Day 60, mortality before hospital discharge, censored on Day 60, VFDs, days free without organ failure, barotrauma between Day 1 and Day 28
Notes	Rescue therapies: prone ventilation, inhaled NO, almitrine bismesylate Discontinued during 18th interim analysis because of absence of 10% absolute reduction in mortality between groups This study was funded by the Centre Hospitalier Universitaire d’Angers
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Study authors performed random allocation in permuted blocks stratified by centre
Allocation concealment (selection bias)	Low risk	Assignment was performed by centralised‐interactive telephone system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Incomplete blinding (blinding of participants but not personnel) but outcomes not influenced
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Main analyses were conducted in a blinded fashion
Incomplete outcome data (attrition bias) All outcomes	Low risk	One participant (control) was excluded because family withdrew consent after randomisation. One participant (intervention) was lost to follow‐up after discharge on Day 29 and was included in the analysis on the basis of the intention‐to‐treat principle
Selective reporting (reporting bias)	Low risk	Published reports included all expected outcomes
Other bias	Low risk	Review authors believed the study to be free of other sources of bias