RIvaroxaban for Valvular Heart diseasE and atRial Fibrillation Trial -RIVER Trial

Hospital do Coracao

Status and phase: Completed; Phase 2

Conditions: Valvular Heart Disease

Treatments: Drug: Rivaroxaban; Drug: Warfarin

Study type: Interventional

Funder types: Other

Identifiers

NCT02303795

RIVER01

Details and patient eligibility

About

RIvaroxaban for Valvular heart diseasE and atRial fibrillation trial (RIVER trial).

Full 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.

Enrollment: 1,005 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male and female patients aged >18 years at time of inclusion

2. Patients with Persistent or paroxysmal Atrial Fibrillation or flutter with bioprosthetic mitral valves.

   • The patient must be able to give informed consent

Exclusion criteria

1. Cardiovascular-related conditions as known presence of cardiac thrombus or tumor

   • Active endocarditis
   • Uncontrolled hypertension

2. Hemorrhage risk-related criteria

   • Active internal bleeding
   • History of, or condition associated with, increased bleeding risk

3. Concomitant conditions and therapies

   • History of previous thromboembolism with high risk of bleeding:

     • 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
     • Acute MI within the last 14 days prior to randomization

   • 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.

   • 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,005 participants in 2 patient groups

Rivaroxaban 20mg

Active Comparator group

Description:

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.

Treatment:

Drug: Warfarin

Drug: Rivaroxaban

Warfarin

Active Comparator group

Description:

Warfarin Warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0.

Treatment:

Drug: Warfarin

Drug: Rivaroxaban