Hodgson 2019.

Study characteristics
Methods	Multi‐centre randomised trial conducted in 35 ICUs from 5 countries (Australia, Ireland, Kingdom of Saudi Arabia, New Zealand, United Kingdom) Time period of study: October 2012 through April 2018
Participants	113 participants aged ≥ 16 (35 centres from 5 countries) Included: patients with moderate to severe ARDS (Berlin definition) who receive MV < 72 hours Excluded: MV longer than 10 days, evidence of barotrauma, active bronchospasm, significant obstructive or restrictive pulmonary disease, any suspicion of raised intracranial pressure, unstable cardiovascular status, pregnant, receiving ECMO or HFO, imminent death, lack of treating physician equipoise Planned sample size of 340 patients allowed 80% power to detect a difference equal to 33% of a standard deviation (equal to 3 VFDs) with a 2‐sided P value of 0.05 and up to 5% withdrawal or loss to long‐term follow‐up. Interim analyses were designed to allow early termination of the trial
Interventions	Control (56): MV assist control, TV 6 mL/kg PBW, plateau pressure ≤ 30 cmH₂O. Respiratory rate ≤ 35 breath/min. Target range for pH 7.30 to 7.45. Target range for oxygenation PaO₂ between 60 and 80 mmHg, SpO₂ between 90% and 95% PEEP: PEEP/FIO₂ combination: mean PEEP 11 cmH₂O during first 72 hours Intervention (57): MV pressure control ventilation (PCV), TV 4 to 6 mL/kg PBW, plateau pressure ≤ 25 to 28 cmH₂O. Respiratory rate ≤ 35 breath/min. Target range for pH 7.15 to 7.45 Target range for oxygenation: PaO₂ between 60 and 80 mmHg, SpO₂ between 90% and 95% PEEP: recruiting manoeuvres followed by decremental PEEP titration until decrease in SpO₂≥ 2% from maximum SpO₂was observed. Mean PEEP 14.7 cmH₂O during first 72 hours
Outcomes	Primary VFD Secondary Physiological outcomes: PaCO₂, PaO₂/FIO₂, PEEP, driving pressure and plateau pressure to Day 7 Clinical outcomes: mortality in ICU, mortality before hospital discharge, mortality at Day 28, mortality at Day 90, mortality at Day 180, use of new hypoxaemic adjuvant therapies, days of MV, LOS in ICU, LOS in hospital Safety outcomes: rate of barotrauma, rate of severe hypotension, new cardiac arrhythmias, desaturation, any related serious adverse events Measurement of serum biomarkers (IL‐6 and IL‐8)
Notes	Discontinued because the PHARLAP study management committee believed that investigators lost equipoise to continue randomisation after publication of the Cavalcanti 2017 study Trial was funded by the National Health and Medical Research Council of Australia, the Health Research Council of New Zealand, the Alfred Health Foundation, the Health Research Board of Ireland, and the Australian and New Zealand College of Anaesthetists
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Study authors used random permuted block schedule
Allocation concealment (selection bias)	Low risk	Assignment was performed by a Web‐based system
Blinding of participants and personnel (performance bias) All outcomes	High risk	In both groups, some treatments (volume optimisation, use of sedation and neuromuscular blockade, timing of tracheostomy and extubation) were at the discretion of the attending physician and were not protocolised
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No blinding but outcomes not influenced by lack of blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	Analysis on the basis of the intention‐to‐treat principle. Representatives of 2 participants (1 assigned to the control group, and 1 assigned to the intervention group) withdrew consent to use study data (not included in the final analysis)
Selective reporting (reporting bias)	Low risk	Published reports included all expected outcomes
Other bias	Low risk	During development of the study, changes were made to inclusion and exclusion criteria. Study authors believe these changes did not modify outcomes