title: Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.
  
  
  METHODS
  Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN88244364.
authors.affiliation: Centre for Infection and Immunity, Queen's University of Belfast, Belfast, BT9 7BL, UK. d.f.mcauley@qub.ac.uk
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: O'Kane
authors.forename: Mark
authors.initials: M
authors.lastname: Cross
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: Lynn
authors.initials: L
authors.lastname: Murphy
authors.forename: Christine
authors.initials: C
authors.lastname: McNally
authors.forename: Grainne
authors.initials: G
authors.lastname: Crealey
authors.forename: Michael
authors.initials: M
authors.lastname: Stevenson
mesh_terms: D055371:Acute Lung Injury / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000401:mortality / Q000503:physiopathology; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D016527:Drug Costs; D017721:Hospital Costs; D017052:Hospital Mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D007494:Ireland; D007902:Length of Stay; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D011446:Prospective Studies; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D012121:Respiration, Artificial; D019821:Simvastatin / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin