Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban (CASTA-DIVA)
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| ClinicalTrials.gov Identifier: NCT02746185 |
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Recruitment Status :
Completed
First Posted : April 21, 2016
Last Update Posted : August 13, 2018
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Sponsor:
Assistance Publique - Hôpitaux de Paris
Collaborator:
Bayer
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasm Venous Thromboembolism | Drug: rivaroxaban Drug: Low-molecular-weight heparin | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 159 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy and Safety of Oral Rivaroxaban for the Treatment of Venous Thromboembolism in Patients With Active Cancer. A Pilot Study. |
| Actual Study Start Date : | September 2016 |
| Actual Primary Completion Date : | April 25, 2018 |
| Actual Study Completion Date : | April 25, 2018 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 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
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Drug: Low-molecular-weight heparin
dalteparin, 200 IU/kg OD for 4 weeks followed by 150 IU/kg OD for 8 weeks
Other Name: dalteparin |
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Experimental: Rivaroxaban
rivaroxaban, orally, 15 mg twice daily for 3 weeks followed by 20 mg once daily for 9 weeks
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Drug: rivaroxaban
rivaroxaban, 15 mg BD (Bis in die) for 3 weeks followed by 20mg OD (Omni die) for 9 weeks
Other Name: xarelto |
Primary Outcome Measures :
- 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
- Unsuspected PE and DVT [ Time Frame: 3 months ]Recurrent VTE during the 3-month treatment period including clinically unsuspected PE and DVT discovered incidentally
- 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
Secondary Outcome Measures :
- Major and clinically significant bleedings during the 3-month treatment period [ Time Frame: 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 [ Time Frame: 3 months ]excluding visceral thrombosis, upper extremity deep vein thrombosis and clinically unsuspected PE and DVT diagnosed incidentally
- Major and non-major clinically significant bleedings at day 90 [ Time Frame: 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.
- Mortality [ Time Frame: 3 months ]
Other Outcome Measures:
- Rivaroxaban plasma concentrations [ Time Frame: 3 months ]Area under the plasma concentration versus time curve (AUC) determined using a liquid chromatography-tandem mass spectrometry method
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02746185
Locations
| France | |
| CHU Amiens - Medecine vasculaire (003) | |
| Amiens, France | |
| CHU Angers - Medecin Interne (002) | |
| Angers, France | |
| Espace Artois Santé | |
| Arras, France | |
| Hopital Saint Andre - Medecine vasculaire (015) | |
| Bordeaux, France | |
| CHU Brest - Departement de medecin interne et pneumologie (008) | |
| Brest, France | |
| CHU Le Bocage - Medecine interne 1 (014) | |
| Dijon, France | |
| CHU Grenoble - Medecine vasculaire (007) | |
| Grenoble, 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, 75015 | |
| Institut Curie - Soins de support en Cancerologie (020) | |
| Paris, France | |
| CHU Saint Etienne - Medecin vasculaire et therapeutique (006) | |
| Saint Etienne, France | |
| Hopital Saine Musse - Service de Medecine Vasculaire (010) | |
| Toulon, France | |
| CHU Rangueil - Medecin Vasculaire (019) | |
| Toulouse, France | |
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Bayer
Investigators
| Principal Investigator: | Guy Meyer, MD | APHP - HEGP |
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT02746185 History of Changes |
| Other Study ID Numbers: |
P141204 |
| First Posted: | April 21, 2016 Key Record Dates |
| Last Update Posted: | August 13, 2018 |
| Last Verified: | August 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
Keywords provided by Assistance Publique - Hôpitaux de Paris:
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cancer venous thromboembolism low-molecular weight heparin rivaroxaban |
Additional relevant MeSH terms:
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Thromboembolism Venous Thromboembolism Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Calcium heparin Heparin Rivaroxaban Heparin, Low-Molecular-Weight Dalteparin |
Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors |