Clinical trial NCT00135876: Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients
Official title: A Trial of Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients (PRODIGE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Brain Tumors
Keywords: deep vein thrombosis
pulmonary embolism
glioma
fragmin
anticoagulant
prophylaxis
dalteparin
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-08-26
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: objectively-proven symptomatic VTE (DVT or PE)
Secondary outcomes:
measure: bleeding (major and all bleeding)
measure: quality of life
measure: cognition assessments
measure: death
Other outcomes:
Locations:
city: Evanston
country: United States
facility: Kellogg Cancer Center - Evanston Northwestern Healthcare
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Kogarah
country: Australia
facility: The St. George Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto-Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Perugia
country: Italy
facility: Università di Perugia
Study officials:
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: James Perry, MD
role: STUDY_CHAIR
affiliation: Ontario Clinical Oncology Group (OCOG)
name: Mark Levine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: William Geerts, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University, Dept of Clinical Epidemiology & Biostatistics
name: Jim Julian, MMath
role: PRINCIPAL_INVESTIGATOR
References: