Meade 2008.

Methods	Randomized controlled trial. Time period of study: August 2000 through March 2006.
Participants	983 participants (30 hospitals). Included: ALI and ARDS (PaO2/FIO2 ≤ 250) during invasive MV. Excluded if: left atrial hypertension, anticipated MV < 48 hours, inability to wean from experimental strategies, severe chronic respiratory disease, neuromuscular disease, intracranial hypertension, morbid obesity, pregnancy, lack of commitment to life support, conditions with expected 6‐month mortality risk > 50%, participation in a confounding trial.
Interventions	Control (508) and intervention (475): MV: ventilator mode: volume‐assist control (intervention), pressure control (control). VT: ≤ 6 mL/kg PBW, plateau pressure ≤ 40 cm H2O (intervention), ≤ 30 cm H2O (control), respiratory rate (breaths/min) ≤ 35, pH ≥ 7.30. Recruiting manoeuvres: intervention group. PEEP. Control: PEEP/FIO2 combination: mean PEEP: 9 cm H2O. Intervention: PEEP/FIO2 combination (programming with higher levels of PEEP): mean PEEP: 12.6 cm H2O. After the first 161 participants, PEEP levels modified in intervention group for the remaining 822 participants, but mean PEEP in all participants in intervention group the same. Target ranges for oxygenation with PEEP/FIO2 combination: PaO2 between 55 and 80 mm Hg; SpO2 between 88% and 93%. Use of rescue therapies1 (both groups) in participants with refractory hypoxaemia (PaO2 < 60 mm Hg for at least 1 hour while receiving an FIO2 of 1.0), refractory acidosis (pH ≤ 7.10 for at least 1 hour), or refractory barotrauma (persistent pneumothorax with two chest tubes on the involved side or increasing subcutaneous or mediastinal emphysema with two chest tubes).
Outcomes	Primary: all‐cause hospital mortality (mortality before hospital discharge). Secondary: mortality during MV, mortality in ICU, mortality at day 28, barotrauma, refractory hypoxaemia, refractory acidosis, refractory barotrauma, use of rescue therapies in response to refractory hypoxaemia, refractory acidosis or refractory barotrauma, days of MV, days of ICU, days of hospitalizations.
Notes	After the first 161 participants, PEEP levels were modified in the intervention group for the remaining 822 participants, but these changes did not alter the outcomes. Rescue therapies: prone ventilation, inhaled NO, high‐frequency oscillation, jet ventilation, extracorporeal membrane oxygenation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Authors used random permuted blocks. Participants randomly allocated.
Allocation concealment (selection bias)	Low risk	Assignment performed by central computerized telephone system. A programming error occurred late that created an unexpected difference in the number of participants allocated to each group, but this problem did not alter the results.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Incomplete blinding (blinding of participants but not of personnel), but the primary outcome was not influenced.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of outcome assessment because one analyst was blinded to allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Analysis on the basis of the intention‐to‐treat principle. Seven participants were withdrawn from the study at various times (ranging from study days 1 to 11).
Selective reporting (reporting bias)	Low risk	Published reports included all expected outcomes.
Other bias	Low risk	A significant difference was noted between the two groups in baseline characteristics for the mean age and rate of sepsis, but these differences were minimal after the data were pooled.