Rheumatic Heart Disease
Conditions
Keywords
atrial fibrillation, stroke
Brief summary
This program is a comprehensive evaluation of rheumatic valvular heart disease (RVHD), Atrial fibrillation (AF)/flutter and stroke. A prospective, randomized, open-label superiority trial comparing rivaroxaban to aspirin in high risk patients either with AF and unsuitable for VKA or without AF and with high risk factors.
Interventions
DRUGRivaroxaban (15 mg)
Rivaroxaban is superior to aspirin for the prevention of the composite of stroke or systemic embolism in patients with RVHD with AF or flutter who are unsuitable for VKA therapy, or in patients with RVHD without AF or Flutter with at least one of the following: 1. Left atrial enlargement ≥ 5.5 cm, OR 2. Left atrial spontaneous echo contrast OR 3. Left atrial thrombus OR 4. Frequent ectopic atrial activity (\>1000/24 hours) on Holter ECG.
DRUGAspirin
Rivaroxaban is superior to aspirin for the prevention of the composite of stroke or systemic embolism in patients with RVHD with AF or flutter who are unsuitable for VKA therapy, or in patients with RVHD without AF or Flutter with at least one of the following: 1. Left atrial enlargement ≥ 5.5 cm, OR 2. Left atrial spontaneous echo contrast OR 3. Left atrial thrombus OR 4. Frequent ectopic atrial activity (\>1000/24 hours) on Holter ECG.
Sponsors
University of Cape Town
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. RVHD diagnosed by echocardiography at any time prior to enrollment 2. Age ≥18 3. Increased risk of stroke by any of the following 1. CHA2DS2-VASc score ≥ 2 OR 2. Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR 3. Left atrial spontaneous echo contrast OR 4. Left atrial thrombus 4. Heart Rhythm 1. 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 2. In the absence of AF or Flutter, patients would be eligible in the presence of any one of the following: <!-- --> 1. Left atrial enlargement ≥5.5 cm OR 2. Left atrial spontaneous echo contrast OR 3. Left atrial thrombus OR 4. Frequent ectopic atrial activity (\>1000/24 hours) on Holter monitoring
Exclusion criteria
1. Refusal to give informed consent 2. Actively involved in any study that would compromise the protocol of INVICTUS Trial 3. Severe co-morbid condition with life expectancy \< 1 year 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 * Allergy to rivaroxaban * Allergy to VKAs ( non-inferiority trial) * Allergy to aspirin ( superiority trial) 8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) \<15 ml/min 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 ≤100 mg per day are not excluded) 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 | Description |
|---|---|---|
| Time from randomization to the first occurrence of Stroke or systemic embolism | Approximately 4 years | Stroke (Ischemic, hemorrhagic or undetermined type) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to the first occurrence of Myocardial Infarction (MI) | Approximately 4 years | — |
| Time from randomization to time of vascular death | Approximately 4 years | Vascular death includes death due to stroke, myocardial infarction, heart failure or cardiogenic shock, sudden death or any other death due to cardiovascular causes. In addition, death due to hemorrhage will be included |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to the first occurrence of a Major bleed | Approximately 4 years | Using the International Society on Thrombosis and Haemostasis (ISTH) major bleeding definition |
Outcome results
None listed