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Prostheses and ImplantsPhase 2/3RIWANCT03566303

Rivaroxaban vs Warfarin in Patients With Metallic Prosthesis

A Phase 2/3 study testing Rivaroxaban 15 mg and Warfarin in people with Prostheses and Implants and Stroke, run by Hospital Geral Roberto Santos at 1 site in Brazil.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Mechanical heart valves (MHV) demand lifelong anticoagulation with vitamin K antagonists (VKA) due to the high thrombogenicity of the prosthesis. Rivaroxaban has previously been tested in experimental and animal models with encouraging results. Read more about this study

Who is it for?
Ages 18 to 74 years
What is being tested?
Rivaroxaban 15 mg and Warfarin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteBrazil
Study dates
10 Jul 2018to 26 Apr 2020
Phase
Phase 2/3
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 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Mechanical prosthetic valve replacement after at least 3 months postoperative

Who cannot join

  • Previous hemorrhagic stroke
  • Ischemic stroke in the last 3 months
  • Severe renal impairment (CrCl rates < 30 ml/min)
  • Active liver disease (any etiology)
  • Concomitant use of any antiplatelet (aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, etc.)
  • Increased risk of bleeding (congenital or acquired)
Show all 11Show fewer
  • Uncontrolled SAH
  • Gastrointestinal hemorrhage within the past year
  • Anemia (Hb level < 10 g/dl) or thrombocytopenia (platelet count < 100 × 109/l)
  • Active infective endocarditis
  • Pregnant or lactating women

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Andre Duraes

    Salvador, Estado de Bahia, 41815000

Other trials in Brazil

About this study

Mechanical heart valves (MHV) demand lifelong anticoagulation with vitamin K antagonists (VKA) due to the high thrombogenicity of the prosthesis. Rivaroxaban has previously been tested in experimental and animal models with encouraging results. The investigators recently sent for publication an experiment with 7 patients who used rivaroxaban in metallic prosthesis with encouraging results. In this way it was decided to do a randomized non-inferiority clinical trial comparing rivaroxaban with warfarin in patients with metallic prosthesis.

Read the detailed description

For patients with severe and symptomatic valvular heart disease, valve replacement surgery improves morbidity and mortality outcomes. It is estimated that four million valve replacement procedures have been performed over the last 50 years and it remains the only definitive treatment for most patients with advanced heart valve disease.1 Patients who received mechanical heart valves (MHV) had a significantly lower mortality, higher cumulative incidence of bleeding and, in some age groups, stroke than did recipients of a biologic prosthesis. In addition, MHV demands lifelong anticoagulation with vitamin K antagonists (VKA), most commonly warfarin, due to the high thrombogenicity of the prosthesis. Even with the appropriate use of therapy, there is a high incidence of thromboembolic events: 1% to 4% per year. Furthermore, bleeding risk is significant, ranging from 2% to 9% per year.4 Indeed, variability in the international normalized ratio (INR) is a major independent predictor of reduced survival in patients with MHV.5 Due to the narrow therapeutic index, interactions, genetic variants, and need for blood monitoring of patients taking VKAs, alternatives to warfarin have now been made available: specifically, inhibitors that directly target Factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, edoxaban).6 RE-ALIGN was a prospective, randomized, phase 2, open-label trial that randomized 252 patients within a 2:1 unblinded fashion to either dabigatran or warfarin, with patients stratified according to interval since replacement (within three to seven days in population A; >three months in population B). Unfortunately, the trial was terminated prematurely because of an excess of thromboembolic and bleeding events among patients in the dabigatran group. The negative results of this study can be explained by the selection of 50 ng/mL as the target dabigatran trough level, the possibility of this drug inducing downstream effects on the coagulation cascade that impair its ability to blunt the postoperative hypercoagulable state relative to warfarin and the inclusion of early postoperative patients (population A) since it is a phase of high incidence of thromboembolic events.

On the other hand, rivaroxaban has already been tested in experimental9 and animal models10 with encouraging results. According to these findings, the investigators hypothesized that a direct Factor Xa inhibitor could be evaluated in patients with MHV for prevention of thromboembolic events.

Being tested
Rivaroxaban 15 mg, Warfarin
Keywords
Valve Heart Disease, Rivaroxaban, Warfarin
Medical subject headings
Stroke, Heart Valve Diseases, Hemostatic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rivaroxaban 15 mgDrug

    Also called Xarelto 15 mg, Rivaroxabana 15 mg

    Rivaroxaban 15 mg BID

  • WarfarinDrug

    Also called Vitamin K antagonist

    Warfarin

Study groups in NCT03566303
Study groupRoleWhat they receive
RivaroxabanActive comparatorRivaroxaban 15mg BID
Receives: Drug: Rivaroxaban 15 mg
WarfarinPlacebo comparatorWarfarin dose adjusted
Receives: Drug: Warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Patients with thromboembolic events: Stroke, transient ischemic attack (TIA), silent brain infarction (SBI) and systemic embolism (SE).

    The primary endpoint was defined as stroke, TIA, SBI and systemic embolism

    Measured: 90 days

  2. major or clinically relevant nonmajor bleeding

    The primary safety outcome was major or clinically relevant nonmajor bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and Bleeding Academic Research Consortium (BARC)

    Measured: 90 days

Secondary outcomes (4)

  1. Patients with e of stroke/TIA/SBI/SE and/or death from any cause.

    Combined outcome

    Measured: 90 days

  2. Cases of myocardial infarction during of follow-up

    Myocardial infarction in the course of treatment

    Measured: 90 days

  3. New cases of valve thrombosis with or without symptoms

    Clinical or asymptomatic valve thrombosis

    Measured: 90 days

  4. New intracardiac thrombus detected at the end of clinical follow-up by transesophageal echocardiogram

    Emergence of intracardiac thrombus seen on transesophageal echocardiogram

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2018
  2. Study start10 Jul 2018
  3. Primary completion26 Apr 2020
  4. Study completion26 Apr 2020

Why it stopped: Coronavirus Pandemic

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)
Masking
Single blind
Who is masked
Investigator
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03566303
Sponsor's protocol ID
90288318.0.0000.5028
Acronym
RIWA
Status last verified
May 2020
First submitted
8 Jun 2018
Last updated
15 May 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Duraes AR, de Souza Lima Bitar Y, Schonhofen IS, Travassos KSO, Pereira LV, Filho JAL, Neto MG, Junior RA, Roever L. Rivaroxaban Versus Warfarin in Patients with Mechanical Heart Valves: Open-Label, Proof-of-Concept trial-The RIWA study. Am J Cardiovasc Drugs. 2021 May;21(3):363-371. doi: 10.1007/s40256-020-00449-3. Epub 2020 Nov 5.

    PubMed 33150497

  • Duraes AR, de Souza Lima Bitar Y, Filho JAL, Schonhofen IS, Camara EJN, Roever L, Cardoso HEDP, Akrami KM. Rivaroxaban versus Warfarin in Patients with Mechanical Heart Valve: Rationale and Design of the RIWA Study. Drugs R D. 2018 Dec;18(4):303-308. doi: 10.1007/s40268-018-0249-5.

    PubMed 30293126

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Rivaroxaban 15 mg and Warfarin in people with Prostheses and Implants and Stroke, run by Hospital Geral Roberto Santos 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 1 inclusion and 11 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: stopped early, as of the sponsor's last update on 15 May 2020. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 was stopped early (reason given: Coronavirus Pandemic). Results are not available in the source record.

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?

Patients with thromboembolic events: Stroke, transient ischemic attack (TIA), silent brain infarction (SBI) and systemic embolism (SE). (time frame: 90 days). The study lists 2 primary outcomes in all. 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 NCT03566303, 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 15 May 2020.

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