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

NCT02832531 | Withdrawn Phase 3 DMC

• 1 other identifier: INVICTUS - ASA
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Keywords

atrial fibrillation; stroke

Outcome Measures

Primary Outcomes (1)

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

  Stroke (Ischemic, hemorrhagic or undetermined type)

  Approximately 4 years

Secondary Outcomes (2)

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

  Approximately 4 years

• Time from randomization to time of vascular death

  Approximately 4 years

Other Outcomes (1)

• Time from randomization to the first occurrence of a Major bleed

  Approximately 4 years

Study Arms (2)

Rivaroxaban (15 mg)

EXPERIMENTAL

Rivaroxaban 15 mg od (n \~ 1000)

Drug: Rivaroxaban (15 mg)

Aspirin (ASA)

ACTIVE COMPARATOR

Aspirin 100 mg od (n\~1000)

Drug: Aspirin

Interventions

Rivaroxaban (15 mg) 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.

Also known as: Xarelto

Rivaroxaban (15 mg)

Aspirin 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.

Also known as: acetylsalicylic acid

Aspirin (ASA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
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• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Population Health Research Institute: lead
• University of Cape Town: collaborator

MeSH Terms

Conditions

Rheumatic Heart Disease; Atrial Fibrillation; Stroke

Interventions

Rivaroxaban; Aspirin

Condition Hierarchy (Ancestors)

Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: July 14, 2016
• Study Start: January 1, 2022
• Primary Completion: April 1, 2022
• Study Completion: August 1, 2022
• Last Updated: July 19, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share