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INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Superiority (INVICTUS-ASA)

Primary Purpose

Rheumatic Heart Disease

Status

Withdrawn

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Rivaroxaban (15 mg)

Aspirin

About this trial

This is an interventional prevention trial for Rheumatic Heart Disease focused on measuring atrial fibrillation, stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

RVHD diagnosed by echocardiography at any time prior to enrollment
Age ≥18
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
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:

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rivaroxaban (15 mg)

Aspirin (ASA)

Arm Description

Rivaroxaban 15 mg od (n ~ 1000)

Aspirin 100 mg od (n~1000)

Outcomes

Primary Outcome Measures

Time from randomization to the first occurrence of Stroke or systemic embolism

Stroke (Ischemic, hemorrhagic or undetermined type)

Secondary Outcome Measures

Time from randomization to the first occurrence of Myocardial Infarction (MI)

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

Full Information

NCT ID

NCT02832531

First Posted

January 7, 2016

Last Updated

July 14, 2022

Sponsor

Population Health Research Institute

Collaborators

University of Cape Town

1. Study Identification

Unique Protocol Identification Number

NCT02832531

Brief Title

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

Acronym

INVICTUS-ASA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Focus on recruitment for non-inferiority trial

Study Start Date

January 2022 (Anticipated)

Primary Completion Date

April 2022 (Anticipated)

Study Completion Date

August 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Population Health Research Institute

Collaborators

University of Cape Town

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatic Heart Disease

Keywords

atrial fibrillation, stroke

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rivaroxaban (15 mg)

Arm Type

Experimental

Arm Description

Rivaroxaban 15 mg od (n ~ 1000)

Arm Title

Aspirin (ASA)

Arm Type

Active Comparator

Arm Description

Aspirin 100 mg od (n~1000)

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban (15 mg)

Other Intervention Name(s)

Xarelto

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Aspirin

Other Intervention Name(s)

acetylsalicylic acid

Intervention Description

Primary Outcome Measure Information:

Title

Time from randomization to the first occurrence of Stroke or systemic embolism

Description

Stroke (Ischemic, hemorrhagic or undetermined type)

Time Frame

Approximately 4 years

Secondary Outcome Measure Information:

Title

Time from randomization to the first occurrence of Myocardial Infarction (MI)

Time Frame

Approximately 4 years

Title

Time from randomization to time of vascular death

Description

Time Frame

Approximately 4 years

Other Pre-specified Outcome Measures:

Title

Time from randomization to the first occurrence of a Major bleed

Description

Using the International Society on Thrombosis and Haemostasis (ISTH) major bleeding definition

Time Frame

Approximately 4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

cumulative participant data only

Learn more about this trial

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

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