Valvular Heart DiseasePhase 2NCT02303795
RIvaroxaban for Valvular Heart diseasE and atRial Fibrillation Trial -RIVER Trial
A Phase 2 study testing Rivaroxaban and Warfarin in people with Valvular Heart Disease, run by Hospital do Coracao at 1 site in Brazil.
Trial summary
RIvaroxaban for Valvular heart diseasE and atRial fibrillation trial (RIVER trial). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Valvular Heart Disease
- What is being tested?
- Rivaroxaban and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,005 participants
- Where
- 1 siteBrazil
- Study dates
- Aug 2015to Aug 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Associação do Sanatório Sírio - Hospital do Coração HCor
São Paulo, São Paulo, 04004050
About this study
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
RIvaroxaban for Valvular heart diseasE and atRial fibrillation trial (RIVER trial).
Read the 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
- Being tested
- Rivaroxaban, Warfarin
- Keywords
- bioprosthetic mitral valve, valvular heart disease, anticoagulant agents, NOACs, rivaroxaban, warfarin
- Medical subject headings
- Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
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.
WarfarinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban 20mg | Active comparator | 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. Receives: Drug: Rivaroxaban; Drug: Warfarin |
| Warfarin | Active comparator | Warfarin Warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0. Receives: Drug: Rivaroxaban; Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (2)
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.
Measured: 12 months
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study startAug 2015
- Primary completionAug 2020
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Valvular Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,005 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital do Coracao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Otavio Berwanger, MD, PhD, Study chair, Hospital do CoracaoRicardo Pavanello, MD, PhD, Study chair, Hospital do CoracaoHelio P Guimarães, MD, PhD, Principal investigator, Hospital do Coracao
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303795
- Sponsor's protocol ID
- RIVER01
- Status last verified
- Apr 2022
- First submitted
- 19 Nov 2014
- Last updated
- 12 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33196155Guimaraes 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.
PubMed 33045224
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02303795
- Acronym / sponsor ID
- RIVER01
- Conditions
- Valvular Heart Disease
- Keywords
- bioprosthetic mitral valve, valvular heart disease, anticoagulant agents, NOACs, rivaroxaban, warfarin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,005 participants (actual)
- Lead sponsor
- Hospital do CoracaoUniversity, hospital or other
- Study start
- Aug 2015 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 1 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban 20mg | Active comparator | Drug: Rivaroxaban, Drug: WarfarinOral 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 | Active comparator | Drug: Rivaroxaban, Drug: WarfarinWarfarin Warfarin once daily (q.d.). The individual doses will be titrated as needed to maintain a target INR of 2.0-3.0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and female patients aged >18 years at time of inclusion
- Patients with Persistent or paroxysmal Atrial Fibrillation or flutter with bioprosthetic mitral valves.
Key exclusion criteria (17 listed)
- Cardiovascular-related conditions as known presence of cardiac thrombus or tumor
- Hemorrhage risk-related criteria
- Concomitant conditions and therapies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivaroxabanPatients 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 | Rivaroxaban 20mg, Warfarin |
| WarfarinPatients 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. | Drug | Rivaroxaban 20mg, Warfarin |
Primary outcome
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.
2 secondary outcomes
Major bleeding
Time frame: 12 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
- Derived from this study: PubMed 33196155Guimaraes 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.
- Derived from this study: PubMed 33045224Guimaraes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Otavio Berwanger, MD, PhD study chair
Hospital do Coracao
Ricardo Pavanello, MD, PhD study chair
Hospital do Coracao
Helio P Guimarães, MD, PhD principal investigator
Hospital do Coracao
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rivaroxaban and Warfarin in people with Valvular Heart Disease, run by Hospital do Coracao at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Clinical Events (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02303795, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.