Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban
- Conditions
- NeoplasmVenous Thromboembolism
- Interventions
- Registration Number
- NCT02746185
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low-molecular-weight heparin 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 Rivaroxaban rivaroxaban rivaroxaban, orally, 15 mg twice daily for 3 weeks followed by 20 mg once daily for 9 weeks
- Primary Outcome Measures
Name Time Method Symptomatic PE 3 months Recurrent VTE during the 3-month treatment period including symptomatic PE
Symptomatic DVT 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)
Worsening of pulmonary vascular or venous obstruction 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 3 months Recurrent VTE during the 3-month treatment period including clinically unsuspected PE and DVT discovered incidentally
- Secondary Outcome Measures
Name Time Method Major and non-major clinically significant bleedings at day 90 3 months Clinically significant non-major bleedings are defined as any bleeding requiring hospitalization or a medical intervention including temporary withholding of anticoagulant treatment to stop bleeding.
Major and clinically significant bleedings during the 3-month treatment period 3 months Major bleeding is defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and includes any bleeding resulting in death; symptomatic bleeding in a critical organ including intracranial, intra spinal, intraocular, retroperitoneal, intra articular and pericardial bleeding and muscle bleeding resulting in compartment syndrome; symptomatic bleeding resulting in a decrease in the hemoglobin concentration of at least 2g/dL or resulting in the transfusion of at least two packs of blood red cells.
Symptomatic recurrences of PE or DVT of the legs 3 months excluding visceral thrombosis, upper extremity deep vein thrombosis and clinically unsuspected PE and DVT diagnosed incidentally
Mortality 3 months
Trial Locations
- Locations (15)
CHU Amiens - Medecine vasculaire (003)
🇫🇷Amiens, France
CHU Saint Etienne - Medecin vasculaire et therapeutique (006)
🇫🇷Saint Etienne, France
Institut Curie - Soins de support en Cancerologie (020)
🇫🇷Paris, France
CHU Angers - Medecin Interne (002)
🇫🇷Angers, France
Hopital Saine Musse - Service de Medecine Vasculaire (010)
🇫🇷Toulon, France
CHU Rangueil - Medecin Vasculaire (019)
🇫🇷Toulouse, France
Espace Artois Santé
🇫🇷Arras, France
CHU Brest - Departement de medecin interne et pneumologie (008)
🇫🇷Brest, France
CHU Grenoble - Medecine vasculaire (007)
🇫🇷Grenoble, France
Hopital Saint Andre - Medecine vasculaire (015)
🇫🇷Bordeaux, France
CHU Le Bocage - Medecine interne 1 (014)
🇫🇷Dijon, France
CH Départemental La Roche sur Yon
🇫🇷La Roche-sur-Yon, France
Centre hospitalier Lyon Sud - Medecine interne (011)
🇫🇷Lyon, France
CHRU de Nîmes - Pneumologie (012)
🇫🇷Nîmes, France
HEGP - Pneumologie et soins intensifs (001)
🇫🇷Paris, France