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

NCT ID: NCT02303795

Last Updated: 2022-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1005 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2020-08-31

Brief Summary

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

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.

Conditions

Valvular Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

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.

Warfarin

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

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.

Warfarin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital do Coracao

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Otavio Berwanger, MD, PhD

Role: STUDY_CHAIR

Hospital do Coracao

Ricardo Pavanello, MD, PhD

Role: STUDY_CHAIR

Hospital do Coracao

Helio P Guimarães, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital do Coracao

Locations

Associação do Sanatório Sírio - Hospital do Coração HCor

São Paulo, São Paulo, Brazil

Countries

Brazil

References

Guimaraes HP, Lopes RD, de Barros E Silva PGM, Liporace IL, Sampaio RO, Tarasoutchi F, Hoffmann-Filho CR, de Lemos Soares Patriota R, Leiria TLL, Lamprea D, Precoma DB, Atik FA, Silveira FS, Farias FR, Barreto DO, Almeida AP, Zilli AC, de Souza Neto JD, Cavalcante MA, Figueira FAMS, Kojima FCS, Damiani L, Santos RHN, Valeis N, Campos VB, Saraiva JFK, Fonseca FH, Pinto IM, Magalhaes CC, Ferreira JFM, Alexander JH, Pavanello R, Cavalcanti AB, Berwanger O; RIVER Trial Investigators. Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve. N Engl J Med. 2020 Nov 26;383(22):2117-2126. doi: 10.1056/NEJMoa2029603. Epub 2020 Nov 14.

Reference Type: DERIVED

PMID: 33196155 (View on PubMed)

Guimaraes HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, Tarasoutchi F, Paixao M, Hoffmann-Filho CR, Patriota R, Leiria TLL, Lamprea D, Precoma DB, Atik FA, Silveira FS, Farias FR, Barreto DO, Almeida AP, Zilli AC, de Souza Neto JD, Cavalcante MA, Figueira FAMS, Junior RA, Moises VA, Mesas CE, Ardito RV, Kalil PSA, Paiva MSMO, Maldonado JGA, de Lima CEB, D'Oliveira Vieira R, Laranjeira L, Kojima F, Damiani L, Nakagawa RH, Dos Santos JRY, Sampaio BS, Campos VB, Saraiva JFK, Fonseca FH, Pinto IM, Magalhaes CC, Ferreira JFM, Lopes RD, Pavanello R, Cavalcanti AB, Berwanger O; RIVER (RIvaroxaban for Valvular Heart diseasE and atRial Fibrillation Trial -RIVER Trial) Investigators. A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial. Am Heart J. 2021 Jan;231:128-136. doi: 10.1016/j.ahj.2020.10.001. Epub 2020 Oct 10.

Reference Type: DERIVED

PMID: 33045224 (View on PubMed)

Other Identifiers

RIVER01

Identifier Type: -

Identifier Source: org_study_id