Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients

A Trial of Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients (PRODIGE)

In patients with malignant glioma, to determine the efficacy of prophylaxis with LMWH (dalteparin) compared to placebo, both commenced beyond the immediate postoperative period, for the prevention of VTE.

Patients are randomized 1:1 to receive dalteparin 5,000 anti-Xa units s.c. daily versus placebo s.c. daily. The primary outcome is VTE-free survival at 6 months. Progression free survival; overall survival, toxicity, and neurocognitive performance are secondary outcome measures.

Inclusion Criteria:

• Both of the following criteria must be satisfied:

  1. Patients with newly-diagnosed pathologically-confirmed WHO Grade 3 or Grade 4 glioma (anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma, and anaplastic mixed glioma). Tumour histology is based on local pathology review only;
  2. Patients 18 years of age or older at time of randomization

Exclusion Criteria:

• If one or more of the following criteria are satisfied, the patient is not eligible for the study:

  1. The presence of acute or chronic DVT demonstrated by duplex ultrasonography (DUS) or venography. (Note: a screening DUS is not required for study entry);
  2. Inability to commence study drug within four weeks of original surgery or biopsy;
  3. Serious hemorrhage requiring hospitalization, transfusion, or surgical intervention within four weeks of potential study entry;
  4. Presence of a coagulopathy (e.g. INR >1.5 or platelet count < 100x109/L);
  5. Symptomatic intracranial or intratumoural bleeding. (Note: post-operative imaging of the brain is not required for study entry. Asymptomatic "routine" post-operative blood products in a post-surgical cavity are not an exclusion;
  6. Known acute (symptomatic or actively bleeding) gastroduodenal ulcer;
  7. Familial bleeding diathesis;
  8. Requiring long term anticoagulants for other reasons (e.g., mechanical heart valves, atrial fibrillation);
  9. Uncontrolled hypertension despite antihypertensive therapy;
  10. Significant renal failure (dependent on dialysis or creatinine of greater than three times upper limit of normal control);
  11. Prior history of documented DVT or PE;
  12. Allergy to anticoagulants (UFH, LMWH) including immune-mediated heparin-induced thrombocytopenia;
  13. Pregnant or of childbearing potential and not using adequate contraception;
  14. Geographically inaccessible for follow-up;
  15. Having an expected life span of less than 6 months;
  16. Body weight < 40 kg.