Rivaroxaban vs Warfarin in Patients With Metallic Prosthesis

Stroke Clinical Trial

— RIWA  

Official title:

Rivaroxaban vs Warfarin in Patients With Metallic Prosthesis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03566303
• Other study ID #: 90288318.0.0000.5028
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: July 10, 2018
• Est. completion date: April 26, 2020

Study information

• Verified date: May 2020
• Source: Hospital Geral Roberto Santos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: April 26, 2020
• Est. primary completion date: April 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Mechanical prosthetic valve replacement after at least 3 months postoperative

Exclusion Criteria:

• 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)

• 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

Related Conditions & MeSH terms

• Anticoagulants and Bleeding Disorders
• Blood Coagulation Disorders
• Heart Diseases
• Heart Valve Diseases
• Hemostatic Disorders
• Prostheses and Implants
• Stroke
• Valve Heart Disease

Intervention

Drug:
• Rivaroxaban 15 mg
Rivaroxaban 15 mg BID
• Warfarin
Warfarin

Locations

Country	Name	City	State
Brazil	Andre Duraes	Salvador	Bahia

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Geral Roberto Santos

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cases of minor bleeding	Any minor bleeding	90 days
Primary	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	90 days
Primary	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)	90 days
Secondary	Patients with e of stroke/TIA/SBI/SE and/or death from any cause.	Combined outcome	90 days
Secondary	Cases of myocardial infarction during of follow-up	Myocardial infarction in the course of treatment	90 days
Secondary	New cases of valve thrombosis with or without symptoms	Clinical or asymptomatic valve thrombosis	90 days
Secondary	New intracardiac thrombus detected at the end of clinical follow-up by transesophageal echocardiogram	Emergence of intracardiac thrombus seen on transesophageal echocardiogram	90 days