Efficacy and Safety of Oral Rivaroxaban for the Treatment of Venous Thromboembolism in Patients With Active Cancer. A Pilot Study.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 159
- Locations
- 15
- Primary Endpoint
- Symptomatic DVT
Study Overview
Brief Summary
The study will compare the efficacy and safety of oral rivaroxaban and subcutaneous dalteparin in patients with cancer associated thrombosis. It is designed as a non-inferiority open label randomized multicenter trial with blinded adjudication of outcome events.
Detailed Description
Patients with active cancer and symptomatic pulmonary embolism, proximal deep vein thrombosis, iliac or caval thrombosis will be randomly assigned to receive either dalteparin using the CLOT regimen or to oral rivaroxaban using the conventional dosage given in the Einstein studies. Experimental and control treatments will be given for three months. The main outcome at three month will include all symptomatic and incidentally discovered venous thromboembolic events including pulmonary embolism (either objectively confirmed and death due to pulmonary embolism), lower limb and upper limb deep vein thrombosis, iliac, caval and visceral thrombosis and any worsening of vascular obstruction which will be collected systematically at inclusion and at day 90. The safety end-points will consist of the rate of major bleedings and the composite of major and non-major but clinically significant bleedings at day 90. All outcome events will be blindly adjudicated by a central independent adjudication committee.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age > 18 years
- •Social security affiliation
- •Written informed consent
- •Solid active cancer, high grade lymphoma or myeloma treated with Immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide). Active cancer is defined as the presence of measurable disease or ongoing (or planned) chemotherapy, radiotherapy or targeted therapy at inclusion.
- •Histologically or cytologically proven cancer.
- •Symptomatic venous thromboembolism objectively confirmed diagnosed because of symptoms or discovered incidentally
- •High-risk of recurrent Venous thromboembolism (VTE) defined by a score of 0 or ≥ 1, using the following criteria: female sex (+1), lung cancer (+1), breast cancer (-1) non metastatic tumor (-2), previous VTE (+1).
Exclusion Criteria
- •Exclusive adjuvant hormonal treatment with no measurable residual disease
- •Sub-segmental isolated pulmonary embolism (PE) without associated proximal DVT
- •Isolated distal deep vein thrombosis (DVT) of the legs
- •Isolated upper-extremity DVT or superior vena cava thrombosis
- •Isolated visceral thrombosis
- •Platelet count < 50 000 G/L
- •Active bleeding
- •Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C
- •Hemostatic defect with contraindication to anticoagulant treatment at therapeutic dosage
- •Vena cava filter at inclusion
- •Fibrinolytic therapy within 3 days preceding inclusion
- •Creatinine clearance < 30 ml/min according to Cockcroft-Gault formula
- •Previous heparin-induced thrombocytopenia
- •Anticoagulant treatment at curative dosage for more than 3 days before inclusion
- •Pregnancy or lack of effective contraceptive treatment for women of childbearing age
- •Treatment with both strong CYP3A4 and P-glycoprotein (PgP) inhibitors: protease inhibitors for HIV disease, systemic ketoconazole
- •Treatment with a strong CYP3A4 inducer: rifampicin, carbamazepine, phenytoin.
- •Life expectancy < 3 months
- •Eastern Cooperative Oncology Group (ECOG) level 3 or 4
Arms & Interventions
Low-molecular-weight heparin
dalteparin, 200 IU/kg subcutaneously once daily for one month followed by 150 IU/kg subcutaneously once daily for 2 months
Intervention: Low-molecular-weight heparin (Drug)
Rivaroxaban
rivaroxaban, orally, 15 mg twice daily for 3 weeks followed by 20 mg once daily for 9 weeks
Intervention: rivaroxaban (Drug)
Outcomes
Primary Outcomes
Symptomatic DVT
Time Frame: 3 months
Recurrent VTE during the 3-month treatment period including all symptomatic DVT (lower limbs distal and proximal DVTs, iliac and caval thrombosis, visceral thrombosis and deep vein thrombosis of the arm)
Symptomatic PE
Time Frame: 3 months
Recurrent VTE during the 3-month treatment period including symptomatic PE
Worsening of pulmonary vascular or venous obstruction
Time Frame: 3 months
Recurrent VTE during the 3-month treatment period including worsening of pulmonary vascular obstruction or venous obstruction on the systematic examinations performed at the end of the 3-month treatment period
Unsuspected PE and DVT
Time Frame: 3 months
Recurrent VTE during the 3-month treatment period including clinically unsuspected PE and DVT discovered incidentally
Secondary Outcomes
- Symptomatic recurrences of PE or DVT of the legs(3 months)
- Major and non-major clinically significant bleedings at day 90(3 months)
- Major and clinically significant bleedings during the 3-month treatment period(3 months)
- Mortality(3 months)