ARDS Network 2000b

Methods	n = 234, 10 centres Allocation concealment: central randomization Baseline similarity: age (A), APACHE III (A), sepsis (A) Blinding: caregivers, study coordinators, investigators Cointerventions: lung protective ventilation studied in factorial design; screening for ability to wean and weaning protocol standardized Withdrawals: none Losses to follow‐up: none
Participants	Inclusions: Mechanical ventilation; AECC definition for ALI and ARDS; duration of ALI or ARDS < 36 hours Exclusions: Neurologic disease impairing weaning; chronic lung disease; morbid obesity; liver disease; immunocompromised; burns; increased intracranial pressure
Interventions	Enteral ketoconazole, 400 mg once daily for 21 days or until 48 hours of unassisted breathing, or placebo
Outcomes	Hospital mortality: RR 1.03 (95% CI 0.84 to 1.29) Ventilator free days to day 28 (median): 10 (ketoconazole group); 9 (placebo group); p = 0.89 Adverse events leading to discontinuation of therapy not reported All adverse events: no difference in incidence of liver enzyme elevations (p = 0.53); trend to more cardiovascular adverse events in ketoconazole group (p = 0.07)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate