Health Condition 1: null- Rheumatic Valvular Heart Disease with either atrial fibrillation or high risk of stroke.
Conditions
Interventions
Intervention1: Rivaroxaban: Oral Rivaroxaban 20 mg daily (in Non-inferiority Trial) for the duration of the study (four years),
Oral Rivaroxaban 15 mg daily (in Superiority Trial) for the duration of
Sponsors
Population Health Research Institute
Eligibility
Inclusion criteria
Inclusion criteria: Non-Inferiority Trial: 1. RVHD diagnosed by echocardiography at any time prior to enrollment 2. Age >=18 3. Increased risk of stroke by any of the following a) CHA2DS2-VASc score >= 2 OR b) Moderate/Severe mitral stenosis with valve area c) Left atrial spontaneous echo contrast OR d) Left atrial thrombus 4. Heart Rhythm a) AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram. Superiority Trial 1. RVHD diagnosed by echocardiography at any time prior to enrollment 2. Age >=18 3. Increased risk of stroke by any of the following a) CHA2DS2-VASc score >= 2 OR b) Moderate/Severe mitral stenosis with valve area c) Left atrial spontaneous echo contrast OR d) Left atrial thrombus 4. Heart Rhythm a) AF or Flutter and unsuitable for VKA therapy. (AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram) OR b) In the absence of AF or Flutter, patients would be eligible in the presence of any one of the following: a. Left atrial enlargement >=5.5 cm OR b. Left atrial spontaneous echo contrast OR c. Left atrial thrombus OR d. Frequent ectopic atrial activity ( >1000/24 hours) on Holter monitoring
Exclusion criteria
Exclusion criteria: For both Non-inferiority and Superiority trials: 1. Refusal to consent 2. Actively involved in any study that would compromise the protocol of INVICTUS Trial 3. Severe co-morbid condition with life expectancy 4. Other serious condition(s) or logistic factors likely to interfere with study participation or with the ability to complete the trial, as appropriate to country or region. 5. Likely to have valve replacement surgery within 6 months 6. Mechanical valve prosthesis or other condition requiring treatment with VKAs. Patients with deep vein thrombosis or recent pulmonary embolism can be enrolled where both VKAs and rivaroxaban are approved. 7. Contraindication to the study medication of the trial a. Allergy to rivaroxaban b. Allergy to VKAs ( non-inferiority trial) c. Allergy to aspirin ( superiority trial) 8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft- Gault) 9. Serious bleeding in the past six months or at high risk for bleeding 10. Moderate to severe hepatic impairment 11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy 12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor. 13. Received an investigational drug in the past 30 days 14. Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits 15. Women who are pregnant and/or breastfeeding 16. Women of child bearing age who do not use an effective form of birth control.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1) Stroke(ischemic, hemorrhagic or undetermined type) 2) Systemic embolismTimepoint: At first one month follow-up, and then every at six month follow-up there after , till four years from randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Myocardial infarction - Hospitalization - Vascular death - Total Death - Composite of stroke, myocardial infarction, systemic embolism, vascular deathTimepoint: At first one month follow-up, and then every at six month follow-up there after , till four years from randomization.;Safety Outcomes: Major Bleeding (ISTH definition) Minor bleedingTimepoint: At first one month follow-up, and then every at six month follow-up there after , till four years from randomization. | — |
Countries
Angola, Botswana, Brazil, Cameroon, China, Egypt, Ethiopia, Guatemala, India, Kazakhstan, Kenya, Kyrgyzstan, Mauritius, Mozambique, Namibia, Nigeria, Pakistan, Paraguay, Philippines, Rwanda, South Africa, Sudan, Uganda, Zambia, Zimbabwe
Contacts
Public ContactDr G Krthikeyan
All India Institute of Medical Scinces
Outcome results
None listed