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. 2013 Jun 6;2013(6):CD009098. doi: 10.1002/14651858.CD009098.pub2

Villar 2006.

Methods Randomized controlled trial. Time period of study: March 1999 through March 2001.
Participants 95 participants, aged > 15. Included: persistent ARDS. Excluded: patients with acute cardiac clinical conditions, pregnancy, neuromuscular diseases, high risk of mortality within 3 months for reasons other than ARDS (severe neurologic damage, age > 80 years, and cancer patients in the terminal stage of their disease), or more than two extrapulmonary organ failures.
Interventions Control (45) and intervention (50): MV: ventilator mode (both groups): volume‐assist control, respiratory rate to maintain PaCO2 between 35 and 50 cm H2O.
Control: VT: 9 to 11 mL/kg PBW, PEEP ≥ 5 cm H2O and FIO2 to optimize SpO2 > 90% and PaO2 between 70 and 100 mm Hg.
Intervention: VT: 5 to 8 mL/kg PBW, PEEP: 2 cm H2O above Pflex or 15 cm H2O if no Pflex; FIO2 to optimize SpO2 > 90% and PaO2 between 70 and 100 mm Hg.
Outcomes Primary: mortality in the ICU.
Secondary: hospital mortality (mortality before hospital discharge), VFD, extrapulmonary organ failure, and barotrauma.
Notes Discontinued prematurely because the absolute mortality difference between control and intervention groups satisfied the stopping rule.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Authors used blocked randomization (restricted randomization) stratified by centre.
Allocation concealment (selection bias) Low risk Opaque sealed envelopes that were randomly ordered.
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Incomplete blinding (blinding of participants but not of personnel), but outcomes not influenced.
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk No blinding, but outcomes not influenced.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Three out of 53 participants missing from intervention group and five out of 50 participants missing from control group, because a centre failed to adhere to the randomization methodology. The final analysis was performed with the remaining 95 participants.
Selective reporting (reporting bias) Low risk Published reports included all expected outcomes.
Other bias Low risk Review author believed the study to be free of other sources of bias.