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

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

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

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.

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.