INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Superiority

Study Overview
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Brief Summary
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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.

Official Title
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INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies

Conditions
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Rheumatic Heart Disease

Intervention / Treatment
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* Drug: Rivaroxaban (15 mg)
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RVHD diagnosed by echocardiography at any time prior to enrollment Age ≥18 Increased risk of stroke by any of the following CHA2DS2-VASc score ≥ 2 OR Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR Left atrial spontaneous echo contrast OR Left atrial thrombus Heart Rhythm 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 In the absence of AF or Flutter, patients would be eligible in the presence of any one of the following: Left atrial enlargement ≥5.5 cm OR Left atrial spontaneous echo contrast OR Left atrial thrombus OR Frequent ectopic atrial activity (>1000/24 hours) on Holter monitoring Exclusion Criteria: Refusal to give informed consent Actively involved in any study that would compromise the protocol of INVICTUS Trial Severe co-morbid condition with life expectancy < 1 year 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. Likely to have valve replacement surgery within 6 months 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. Contraindication to the study medication of the trial Allergy to rivaroxaban Allergy to VKAs ( non-inferiority trial) Allergy to aspirin ( superiority trial) Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) <15 ml/min Serious bleeding in the past six months or at high risk for bleeding Moderate to severe hepatic impairment Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy ≤100 mg per day are not excluded) Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor. Received an investigational drug in the past 30 days Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits Women who are pregnant and/or breastfeeding Women of child bearing age who do not use an effective form of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban (15 mg)<br>Rivaroxaban 15 mg od (n   1000) | Drug: Rivaroxaban (15 mg)<br>* 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: Left atrial enlargement ≥ 5.5 cm, OR Left atrial spontaneous echo contrast OR Left atrial thrombus OR Frequent ectopic atrial activity (>1000/24 hours) on Holter ECG.<br>* Other names: Xarelto;|
| Active Comparator: Aspirin (ASA)<br>Aspirin 100 mg od (n 1000) | Drug: Aspirin<br>* 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: Left atrial enlargement ≥ 5.5 cm, OR Left atrial spontaneous echo contrast OR Left atrial thrombus OR Frequent ectopic atrial activity (>1000/24 hours) on Holter ECG.<br>* Other names: acetylsalicylic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomization to the first occurrence of Stroke or systemic embolism | Stroke (Ischemic, hemorrhagic or undetermined type) | Approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomization to the first occurrence of Myocardial Infarction (MI) |  | Approximately 4 years | 
| Time from randomization to time of vascular death | 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 | Approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, stroke