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

Primary Purpose

Valvular Heart Disease

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Rivaroxaban
Warfarin
Sponsored by
Hospital do Coracao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Valvular Heart Disease focused on measuring bioprosthetic mitral valve, valvular heart disease, anticoagulant agents, NOACs, rivaroxaban, warfarin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Associação do Sanatório Sírio - Hospital do Coração HCor

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Rivaroxaban 20mg

Warfarin

Arm 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.

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

Outcomes

Primary Outcome Measures

Major Clinical Events
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

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

Full Information

First Posted
November 19, 2014
Last Updated
April 4, 2022
Sponsor
Hospital do Coracao
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1. Study Identification

Unique Protocol Identification Number
NCT02303795
Brief Title
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

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital do Coracao

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Valvular Heart Disease
Keywords
bioprosthetic mitral valve, valvular heart disease, anticoagulant agents, NOACs, rivaroxaban, warfarin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1005 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rivaroxaban 20mg
Arm Type
Active Comparator
Arm 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.
Arm Title
Warfarin
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Intervention Description
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
Intervention Name(s)
Warfarin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Major Clinical Events
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Major bleeding
Description
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.
Time Frame
12 months
Title
Combined endpoint of nonfatal stroke (CVA), transient ischemic attack (TIA), systemic embolism, valve thrombosis, venous thromboembolism and vascular causes death.thrombosis, and vascular death
Description
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
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients aged >18 years at time of inclusion Patients with Persistent or paroxysmal Atrial Fibrillation or flutter with bioprosthetic mitral valves. The patient must be able to give informed consent Exclusion Criteria: Cardiovascular-related conditions as known presence of cardiac thrombus or tumor Active endocarditis Uncontrolled hypertension Hemorrhage risk-related criteria Active internal bleeding History of, or condition associated with, increased bleeding risk 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Otavio Berwanger, MD, PhD
Organizational Affiliation
Hospital do Coracao
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ricardo Pavanello, MD, PhD
Organizational Affiliation
Hospital do Coracao
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Helio P Guimarães, MD, PhD
Organizational Affiliation
Hospital do Coracao
Official's Role
Principal Investigator
Facility Information:
Facility Name
Associação do Sanatório Sírio - Hospital do Coração HCor
City
São Paulo
State/Province
SP
ZIP/Postal Code
04004050
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
33196155
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.
Results Reference
derived
PubMed Identifier
33045224
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.
Results Reference
derived

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

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