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

• ClinicalTrials.gov Identifier: NCT02303795
• Recruitment Status: Active, not recruiting
• First Posted: December 1, 2014
• Last Update Posted: July 29, 2019
• Sponsor: Hospital do Coracao
• Information provided by (Responsible Party): Hospital do Coracao

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Valvular Heart Disease	Drug: Rivaroxaban; Drug: Warfarin	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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1005 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: August 2015
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

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 :

1. Major Clinical Events [ Time Frame: 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 :

1. Major bleeding [ Time Frame: 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.
2. Combined endpoint of nonfatal stroke (CVA), transient ischemic attack (TIA), systemic embolism, valve thrombosis, venous thromboembolism and vascular causes death.thrombosis, and vascular death [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Brazil

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Guimarães 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, Magalhães 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.

Guimarães HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, Tarasoutchi F, Paixão 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, Moisés 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, Magalhães 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.

• Responsible Party: Hospital do Coracao
• ClinicalTrials.gov Identifier: NCT02303795
• Other Study ID Numbers: RIVER01
• First Posted: December 1, 2014
• Last Update Posted: July 29, 2019
• Last Verified: July 2019

Keywords provided by Hospital do Coracao:

bioprosthetic mitral valve; valvular heart disease; anticoagulant agents; NOACs; rivaroxaban; warfarin

Additional relevant MeSH terms:

Atrial Fibrillation; Heart Diseases; Heart Valve Diseases; Arrhythmias, Cardiac; Cardiovascular Diseases; Pathologic Processes; Warfarin; Rivaroxaban; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action