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

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:

• 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;
• 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:

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