Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BackgroundStudies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.MethodsIn this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.ResultsThe study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.ConclusionsSimvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).

Original publication





The New England journal of medicine

Publication Date





1695 - 1703


From the Centre for Infection and Immunity, Queen's University of Belfast (D.F.M., C.M.O.), the Regional Intensive Care Unit (D.F.M., B.M.) and Northern Ireland Clinical Trials Unit (D.F.M., C. McDowell, C. McNally), Royal Victoria Hospital, and the Intensive Care Unit, Ulster Hospital (T.J.T.), Belfast, the Heart of England National Health Service (NHS) Foundation Trust, Birmingham (G.D.P.), Warwick Medical School Clinical Trials Unit, University of Warwick, Warwick (G.D.P.), the Intensive Care Unit, Antrim Area Hospital, Antrim (P.J.), the Critical Care Units, King's Health Partners (King's College Hospital), London (P.A.H.), and the John Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.J.J.) - all in the United Kingdom; the Department of Anaesthesia, School of Medicine, Health Research Board Galway Clinical Research Facility, Clinical Sciences Institute, National University of Ireland, Galway, Ireland (J.G.L.); and the Department of Anesthesia, Centre for Critical Care Research, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (J.G.L.).


HARP-2 Investigators, Irish Critical Care Trials Group, Humans, Simvastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Tidal Volume, Treatment Failure, Combined Modality Therapy, Respiration, Artificial, Double-Blind Method, Adult, Aged, Middle Aged, Intensive Care Units, Female, Male, Kaplan-Meier Estimate, Respiratory Distress Syndrome