Meduri 2007

Methods	Randomized controlled trial (2:1 scheme) 5 centres
Participants	Adults (n = 91) with early ARDS (≤ 72 hours from diagnosis of ARDS). 61 (67%) had sepsis or septic shock, and the primary author provided separate data for these participants Stratification according to cortisol response to 250 µg Synacthene into non‐responders (delta cortisol ≤ 9 µg/dL) and responders (> 9 µg/dL)
Interventions	Methylprednisolone loading dose of 1 mg/kg followed by continuous infusion of 1 mg/kg/d from day 1 to day 14, then 0.5 mg/kg/d from day 15 to day 21, then 0.25 mg/kg/d from day 22 to day 25, then 0.125 mg/kg/d from day 26 to day 28. If participant was extubated before day 14, he/she was advanced to day 15 of drug therapy. Treatment was given intravenously until enteral intake was restored, then was given as a single oral dose Placebo
Outcomes	PRIMARY Improvement in Lung Injury Score (LIS) at day 7. This improvement was defined as a reduction in score ≥ 1 point and a day 7 score ≤ 2 (if randomization LIS score < 3) or ≤ 2.5 (if randomization LIS score < 3) SECONDARY Mechanical ventilation‐free days Multiple organ dysfunction (MOD) score at study day 7 28‐Day mortality ICU mortality Hospital mortality Length of stay in ICU and at hospital C‐reactive protein levels at study day 7 Safety
Notes	If participant failed to improve on Lung Injury Score between day 7 and day 9, he/she received open‐label methylprednisolone at 2 mg/kg/d for unresolving ARDS Study location: USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomization scheme
Allocation concealment (selection bias)	Low risk	Centralized randomization
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants: yes Care‐givers: yes Data collectors: yes Outcome assessors: yes Data analysts: yes
Incomplete outcome data (attrition bias) All outcomes	Low risk	Full access to data excluding any attrition bias
Selective reporting (reporting bias)	High risk	Study was stopped prematurely for efficacy
Other bias	Low risk	Full access to data including screening log