title: Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction--a randomised placebo-controlled trial (KARE): study protocol.
abstract: BACKGROUND
  Acute lung injury is a common, devastating clinical syndrome associated with substantial mortality and morbidity with currently no proven therapeutic interventional strategy to improve patient outcomes. The objectives of this study are to test the potential therapeutic effects of keratinocyte growth factor for patients with acute lung injury on oxygenation and biological indicators of acute inflammation, lung epithelial and endothelial function, protease:antiprotease balance, and lung extracellular matrix degradation and turnover.
  
  
  METHODS
  This will be a prospective, randomised, double-blind, allocation-concealed, placebo-controlled, phase 2, multicentre trial. Randomisation will be stratified by presence of severe sepsis requiring vasopressors. Patients in an ICU fulfilling the American-European Consensus Conference Definition of acute lung injury will be randomised in a 1:1 ratio to receive an intravenous bolus of either keratinocyte growth factor (palifermin, 60 μg/kg) or placebo (0.9% sodium chloride solution) daily for a maximum of 6 days. The primary endpoint of this clinical study is to evaluate the efficacy of palifermin to improve the oxygenation index at day 7 or the last available oxygenation index prior to patient discontinuation from the study.A formal statistical analysis plan has been constructed. Analyses will be carried out on an intention-to-treat basis. A single analysis is planned at the end of the trial. P = 0.05 will be considered statistically significant and all tests will be two-sided. For continuously distributed outcomes, differences between groups will be tested using independent-sample t tests, analysis of variance and analysis of covariance with transformation of variables to normality or nonparametric equivalents. The trial will be reported in line with the Consolidated Standards of Reporting Trials (Consort 2010 guidelines).
  
  
  BACKGROUND
  ISRCTN95690673.
authors: Centre for Infection and Immunity, The Queen's University of Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
authors: Laurence J M
authors: LJ
authors: Cross
authors: Cecilia M
authors: CM
authors: O'Kane
authors: Cliona
authors: C
authors: McDowell
authors: Jospeh J
authors: JJ
authors: Elborn
authors: Michael A
authors: MA
authors: Matthay
authors: Daniel F
authors: DF
authors: McAuley
mesh_terms: D055371:Acute Lung Injury / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002985:Clinical Protocols; D004311:Double-Blind Method; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007362:Intensive Care Units; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008170:Lung Compliance; D009660:Northern Ireland; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D012123:Pulmonary Ventilation; D020127:Recovery of Function; D012107:Research Design; D012121:Respiration, Artificial; D018805:Sepsis / Q000209:etiology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D051523:Fibroblast Growth Factor 7