Clinical trial NCT02832531: INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Superiority
Official title: INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Rheumatic Heart Disease
Keywords: atrial fibrillation
stroke
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2016-07-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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:

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   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.

Primary outcomes:
measure: Time from randomization to the first occurrence of Stroke or systemic embolism
timeFrame: Approximately 4 years
Secondary outcomes:
measure: Time from randomization to the first occurrence of Myocardial Infarction (MI)
timeFrame: Approximately 4 years
measure: Time from randomization to time of vascular death
timeFrame: Approximately 4 years
Other outcomes:
measure: Time from randomization to the first occurrence of a Major bleed
timeFrame: Approximately 4 years
Locations:
Study officials:
References: