RIvaroxaban for Valvular Heart diseasE and atRial Fibrillation Trial -RIVER Trial
Study Details
Study Description
Brief Summary
RIvaroxaban for Valvular heart diseasE and atRial fibrillation trial (RIVER trial).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
A Phase 2, Randomized, Open label, Non-Inferiority Clinical Trial to Explore the Safety and Efficacy of Rivaroxaban compared with vitamin K antagonism in Patients with Atrial Fibrillation with Bioprosthetic Mitral valves - RIVER. Main analysis for the primary endpoint are based on the Restricted Mean Survival Time (RMST) method.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Rivaroxaban 20mg Oral Rivaroxaban, 20 mg od. Patients with a calculated creatinine clearance of 30 to 49 mL/min per 1.73 m2 received a reduced dose of rivaroxaban of 15 mg od. |
Drug: Rivaroxaban
Patients assigned to rivaroxaban will receive oral rivaroxaban, 20 mg od. Patients with a calculated creatinine clearance of 30 to 49 mL/min per 1.73 m2 received a reduced dose of rivaroxaban of 15 mg od.
Drug: Warfarin
Patients will take the warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0.
Patients with 65 > years old, should take warfarin (2,5mg/day) and all others patients should take 5mg/day.
|
| Active Comparator: Warfarin Warfarin Warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0. |
Drug: Rivaroxaban
Patients assigned to rivaroxaban will receive oral rivaroxaban, 20 mg od. Patients with a calculated creatinine clearance of 30 to 49 mL/min per 1.73 m2 received a reduced dose of rivaroxaban of 15 mg od.
Drug: Warfarin
Patients will take the warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0.
Patients with 65 > years old, should take warfarin (2,5mg/day) and all others patients should take 5mg/day.
|
Outcome Measures
Primary Outcome Measures
- Major Clinical Events [12 months]
Combined Endpoint of major clinical events as defined by strokes (CVA), transient ischemic attack (TIA), major bleeding, all-cause death, valve thrombosis and non-CNS systemic embolism, hospitalization due to cardiac failure.
Secondary Outcome Measures
- Major bleeding [12 months]
Clinically overt bleeding associated with: fatal outcome, involving a critical site, or clinically overt bleeding associated with a fall in hemoglobin concentration of ≥2 g/dL, or leading to transfusion of ≥2 units of packed red blood cells or whole blood.
- Combined endpoint of nonfatal stroke (CVA), transient ischemic attack (TIA), systemic embolism, valve thrombosis, venous thromboembolism and vascular causes death.thrombosis, and vascular death [12 months]
Stroke: sudden, focal neurologic deficit from a presumed cerebrovascular cause, not reversible within 24 hours and not due to na identifiable cause. Non-CNS systemic embolism: abrupt vascular insufficiency associated with clinical or radiologic evidence of arterial occlusion. Valve thrombosis: any thrombus attached to or near an implanted valve that occludes part of the blood flow, interferes with function or warrant treatment. Mortality: Deaths any cause. Venous thromboembolism: verification by definitive diagnostic evaluation. Deep Vein Thrombosis: abnormal compression ultrasound or intraluminal filling defect on venography or autopsy. Pulmonary embolism: at least one: 1) intraluminal filling defect on CT scan; 2) intraluminal filling defect on pulmonary angiogram; 3) high- probability on v/p lung scan; 4)inconclusive spiral CT, pulmonary image with demonstration of DVT in the lower extremities; 5) autopsy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female patients aged >18 years at time of inclusion
-
Patients with Persistent or paroxysmal Atrial Fibrillation or flutter with bioprosthetic mitral valves.
- The patient must be able to give informed consent
Exclusion Criteria:
- Cardiovascular-related conditions as known presence of cardiac thrombus or tumor
-
Active endocarditis
-
Uncontrolled hypertension
- Hemorrhage risk-related criteria
-
Active internal bleeding
-
History of, or condition associated with, increased bleeding risk
- Concomitant conditions and therapies
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History of previous thromboembolism with high risk of bleeding:
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Severe, disabling stroke (modified Rankin score of 4-5, inclusive) within 3 months
-
Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to randomization
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Acute MI within the last 14 days prior to randomization
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Treatment with: Chronic aspirin therapy > 100 mg daily or dual antiplatelet therapy; Intravenous antiplatelets; Fibrinolytics; Anticipated need for long-term treatment with a nonsteroidal antiinflammatory drug; Systemic treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease inhibitors; Treatment with a strong inducer of cytochrome P450 3A4, such as rifampicin, phenytoin, phenobarbital, or carbamazepine.
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Anemia
-
Pregnancy or breastfeeding or women of reproductive age not using effective contraceptive methods
-
Calculated creatinine clearance bellow 30 mL/min
-
Known significant liver disease or alanine aminotransferase N3× the upper limit of normal
-
Previous participation in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Associação do Sanatório Sírio - Hospital do Coração HCor | São Paulo | SP | Brazil | 04004050 |
Sponsors and Collaborators
- Hospital do Coracao
Investigators
- Study Chair: Otavio Berwanger, MD, PhD, Hospital do Coracao
- Study Chair: Ricardo Pavanello, MD, PhD, Hospital do Coracao
- Principal Investigator: Helio P Guimarães, MD, PhD, Hospital do Coracao
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RIVER01