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

NCT ID: NCT02832531

Last Updated: 2022-07-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-31
• Study Completion Date: 2022-08-31

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.

Conditions

Rheumatic Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Rivaroxaban (15 mg)

Rivaroxaban 15 mg od (n \~ 1000)

Group Type: EXPERIMENTAL

Rivaroxaban (15 mg)

Intervention Type: DRUG

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.

Aspirin (ASA)

Aspirin 100 mg od (n\~1000)

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

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.

Interventions

Rivaroxaban (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.

Intervention Type: DRUG

Aspirin

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.

Intervention Type: DRUG

Other Intervention Names

Xarelto; acetylsalicylic acid

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cape Town

OTHER

Sponsor Role: collaborator

Population Health Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

INVICTUS - ASA

Identifier Type: -

Identifier Source: org_study_id