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INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Non-Inferiority (INVICTUS-VKA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02832544
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : April 26, 2019
University of Cape Town
Information provided by (Responsible Party):
Population Health Research Institute

Brief Summary:

This program is a comprehensive evaluation of rheumatic valvular heart disease (RVHD), Atrial fibrillation (AF)/flutter and stroke.

A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard vitamin K antagonists (VKA) therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied.

Condition or disease Intervention/treatment Phase
Rheumatic Heart Disease Drug: Rivaroxaban (20 mg) Drug: Vitamin K antagonists (VKA) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies
Actual Study Start Date : August 22, 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : October 2020

Arm Intervention/treatment
Experimental: Rivaroxaban (20 mg)
Rivaroxaban 20 mg od (n ~ 2250); 15 mg od (once daily) in patients with creatinine clearance (CrCl) 15-49 ml/min
Drug: Rivaroxaban (20 mg)
Rivaroxaban is non-inferior to VKAs for the prevention of stroke or systemic embolism in patients with AF/flutter and RVHD and potentially superior to VKAs.
Other Name: Xarelto

Active Comparator: Vitamin K antagonists (VKA)
Any approved VKA in the participating country (n ~ 2250); VKA titrated to achieve an INR of 2.0-3.0
Drug: Vitamin K antagonists (VKA)
Other Name: Warfarin

Primary Outcome Measures :
  1. Time from randomization to the first occurrence of Stroke or Systemic Embolism [ Time Frame: Approximately 4 years ]
    Stroke (Ischemic, hemorrhagic or undetermined type)

Secondary Outcome Measures :
  1. Time from randomization to the first occurrence of Myocardial Infarction (MI) [ Time Frame: Approximately 4 years ]
  2. Time from randomization to time of vascular death [ Time Frame: Approximately 4 years ]
    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

Other Outcome Measures:
  1. Time from randomization to the first occurrence of a Major Bleed [ Time Frame: Approximately 4 years ]
    using the ISTH major bleeding definition

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

    • 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
  4. Heart Rhythm *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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02832544

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Contact: Gayle D Lewis 1-866-414-7474
Contact: Sumathy Rangarajan, MSc 1-866-414-7474

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Sponsors and Collaborators
Population Health Research Institute
University of Cape Town
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Principal Investigator: Stuart Connolly, MD Population Health Research Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Population Health Research Institute Identifier: NCT02832544    
Other Study ID Numbers: INVICTUS - VKA
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: cumulative participant data only
Keywords provided by Population Health Research Institute:
atrial fibrillation
Additional relevant MeSH terms:
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Rheumatic Heart Disease
Rheumatic Diseases
Heart Diseases
Cardiovascular Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Rheumatic Fever
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vitamin K
Growth Substances
Physiological Effects of Drugs
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifibrinolytic Agents
Fibrin Modulating Agents