title: PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.
abstract: OBJECTIVE
  Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients.
  
  
  METHODS
  Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment.
  
  
  RESULTS
  The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48).
  
  
  CONCLUSIONS
  Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.
authors.affiliation: Division of Neurology, Sunnybrook Health Science Centre, Toronto Ontario, Canada. james.perry@sunnybrook.ca
authors.forename: J R
authors.initials: JR
authors.lastname: Perry
authors.forename: J A
authors.initials: JA
authors.lastname: Julian
authors.forename: N J
authors.initials: NJ
authors.lastname: Laperriere
authors.forename: W
authors.initials: W
authors.lastname: Geerts
authors.forename: G
authors.initials: G
authors.lastname: Agnelli
authors.forename: L R
authors.initials: LR
authors.lastname: Rogers
authors.forename: M G
authors.initials: MG
authors.lastname: Malkin
authors.forename: R
authors.initials: R
authors.lastname: Sawaya
authors.forename: R
authors.initials: R
authors.lastname: Baker
authors.forename: A
authors.initials: A
authors.lastname: Falanga
authors.forename: S
authors.initials: S
authors.lastname: Parpia
authors.forename: T
authors.initials: T
authors.lastname: Finch
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D017985:Dalteparin / Q000627:therapeutic use*; D015951:Factor Xa / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D012306:Risk; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000628:therapy
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010919:Placebos; D015951:Factor Xa; D017985:Dalteparin