title: A double-blind, randomized controlled trial of the prevention of clinically important venous thromboembolism after isolated lower leg fractures.
abstract: BACKGROUND
  Among patients with isolated below-knee fractures, previous studies have detected asymptomatic deep vein thrombosis in 10%-40% using contrast venography. However, the clinical relevance of these thrombi is unknown; there is considerable uncertainty about the risk: benefit of routine thromboprophylaxis and clinical practice guidelines differ in their recommendations.
  
  
  METHODS
  In this multicenter, double-blind trial, 265 patients with isolated lower leg fractures requiring surgery were randomized to subcutaneous dalteparin 5000 units or matching placebo once daily for 2 weeks with bilateral Doppler ultrasound (DUS) of the proximal leg veins on postoperative day 14±2 and 3-month follow-up. The primary effectiveness outcome was clinically important venous thromboembolism (CIVTE), defined as the composite of symptomatic venous thromboembolism within 3 months after surgery and asymptomatic proximal deep vein thrombosis on DUS. The primary safety outcome was major bleeding.
  
  
  RESULTS
  Two hundred fifty-eight patients (97%) were included in the primary outcome analysis for effectiveness (130: dalteparin; 128: placebo). Incidence of CIVTE in the dalteparin and placebo groups was 1.5% and 2.3%, respectively (absolute risk reduction, 0.8%; 95% confidence interval, -2.0 to 3.0). There were no fatal pulmonary emboli or major bleeding.
  
  
  CONCLUSIONS
  The overall incidence of CIVTE after surgically repaired, isolated tibia, fibula, and ankle fractures was low (1.9%; 95% confidence interval, 0.7-4.7), with no observed differences between dalteparin and placebo either for CIVTE or safety. Recruitment was stopped at the first interim analysis. This study also demonstrates the substantial discrepancy in venous thromboembolism rates between trials that use venographic outcomes compared with more clinically relevant outcomes.
  
  
  METHODS
  Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Departments of *Medicine, †Clinical Pathology, and ‡Surgery, Sunnybrook Health Sciences Center, University of Toronto, Ontario, Canada; and §Department of Medicine, McMaster University, Ontario, Canada.
authors.forename: Rita
authors.initials: R
authors.lastname: Selby
authors.forename: William H
authors.initials: WH
authors.lastname: Geerts
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Kreder
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
authors.forename: Lisa
authors.initials: L
authors.lastname: Kaus
authors.forename: Faith
authors.initials: F
authors.lastname: Sealey
mesh_terms: D000328:Adult; D000368:Aged; D064386:Ankle Fractures / Q000150:complications / Q000601:surgery; D000925:Anticoagulants / Q000627:therapeutic use*; D017985:Dalteparin / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005360:Fibula / Q000293:injuries / Q000601:surgery; D050723:Fractures, Bone / Q000150:complications* / Q000601:surgery; D006801:Humans; D007869:Leg Injuries / Q000150:complications / Q000000981:diagnostic imaging / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D013978:Tibial Fractures / Q000150:complications / Q000601:surgery; D014463:Ultrasonography; D054556:Venous Thromboembolism / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017985:Dalteparin