Focus on recruitment for non-inferiority trial

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.

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.

cumulative participant data only