Clinical trial NCT02303795: RIvaroxaban for Valvular Heart diseasE and atRial Fibrillation Trial -RIVER Trial
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Valvular Heart Disease
Keywords: bioprosthetic mitral valve
valvular heart disease
anticoagulant agents
NOACs
rivaroxaban
warfarin
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
First posted: 2014-12-01
Enrollment: 1005
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Major Clinical Events
timeFrame: 12 months
Secondary outcomes:
measure: Major bleeding
timeFrame: 12 months
measure: Combined endpoint of nonfatal stroke (CVA), transient ischemic attack (TIA), systemic embolism, valve thrombosis, venous thromboembolism and vascular causes death.thrombosis, and vascular death
timeFrame: 12 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Associação do Sanatório Sírio - Hospital do Coração HCor
state: SP
Study officials:
affiliation: Hospital do Coracao
name: Otavio Berwanger, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Ricardo Pavanello, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Helio P Guimarães, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.