title: PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan.
abstract: BACKGROUND
  This article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) before dissemination of results. PROphylaxis for ThromboEmbolism in Critical Care Trial (NCT00182143) is a randomized, stratified, concealed international trial comparing subcutaneous injection of unfractionated heparin (UFH) 5000 IU or the low-molecular weight heparin (LMWH) dalteparin 5000 IU once daily plus once-daily placebo for the duration of the intensive care unit stay.
  
  
  METHODS
  The objective of PROTECT is to examine, among medical-surgical critically ill patients, the effect of the LMWH vs heparin on the primary outcome of proximal leg deep vein thrombosis (DVT) and the following secondary outcomes: DVT elsewhere, pulmonary embolism, any venous thromboembolism (DVT or pulmonary embolism), the composite of venous thromboembolism or death, bleeding, and heparin-induced thrombocytopenia. Patients are followed up to death or hospital discharge. Venous thromboembolism events were included after intensive care unit discharge. All patients, families, clinicians, research personnel, and the trial biostatistician are blind to allocation.
  
  
  RESULTS
  We describe the pilot work, large trial methodology, implementation methods, and the analytic plan. Patient recruitment is complete, but 2 patients remain in the hospital. The rigorous design of PROTECT suggests that the risk of systematic error will be low. The sample size suggests that the risk of random error will be low. PROTECT will be the largest investigator-initiated peer-review funded thromboprophylaxis trial in critical care in the world.
  
  
  CONCLUSIONS
  If PROTECT shows that LMWH is more effective than UFH, this trial will change practice in that LMWH may be the anticoagulant thromboprophylaxis of choice for this population. If the results show that UFH is as effective or more effective than LMWH, intensivists in many parts of the world may continue to use UFH, whereas those currently using LMWH may reconsider and change to use UFH. Unfavorable consequences such as major bleeding, ease of use, and the costs of complications will also factor into such decisions.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. debcook@mcmaster.ca
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: William
authors.initials: W
authors.lastname: Geerts
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: D Jamie
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Nicole
authors.initials: N
authors.lastname: Zytaruk
authors.forename: Shirley
authors.initials: S
authors.lastname: Vallance
authors.forename: Otavio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rocha
authors.forename: Ismael
authors.initials: I
authors.lastname: Qushmaq
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
mesh_terms: D003422:Critical Care; D017985:Dalteparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D007362:Intensive Care Units; D015337:Multicenter Studies as Topic; D011655:Pulmonary Embolism / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D020246:Venous Thrombosis / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D006493:Heparin; D017985:Dalteparin