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

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ClinicalTrials.gov Identifier: NCT02832544
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : April 26, 2019
Sponsor:
Collaborators:
University of Cape Town
Bayer
Information provided by (Responsible Party):
Population Health Research Institute

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE July 14, 2016
Last Update Posted Date April 26, 2019
Actual Study Start Date  ICMJE August 22, 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
Time from randomization to the first occurrence of Stroke or Systemic Embolism [ Time Frame: Approximately 4 years ]
Stroke (Ischemic, hemorrhagic or undetermined type)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02832544 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
  • Time from randomization to the first occurrence of Myocardial Infarction (MI) [ Time Frame: Approximately 4 years ]
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 11, 2016)
Time from randomization to the first occurrence of a Major Bleed [ Time Frame: Approximately 4 years ]
using the ISTH major bleeding definition
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Non-Inferiority
Official Title  ICMJE INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Rheumatic Heart Disease
Intervention  ICMJE
  • 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
  • Drug: Vitamin K antagonists (VKA)
    Other Name: Warfarin
Study Arms  ICMJE
  • 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
    Intervention: Drug: Rivaroxaban (20 mg)
  • 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
    Intervention: Drug: Vitamin K antagonists (VKA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2016)
4500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gayle D Lewis 1-866-414-7474 gayle.lewis@phri.ca
Contact: Sumathy Rangarajan, MSc 1-866-414-7474 sumathy.rangarajan@phri.ca
Listed Location Countries  ICMJE Kazakhstan,   Botswana,   Brazil,   Cameroon,   China,   Egypt,   Ethiopia,   India,   Kenya,   Kyrgyzstan,   Malawi,   Mexico,   Mozambique,   Nepal,   Nigeria,   Pakistan,   Paraguay,   Philippines,   Rwanda,   South Africa,   Sudan,   Tanzania,   Uganda,   Zambia,   Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02832544
Other Study ID Numbers  ICMJE INVICTUS - VKA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: cumulative participant data only
Responsible Party Population Health Research Institute
Study Sponsor  ICMJE Population Health Research Institute
Collaborators  ICMJE
  • University of Cape Town
  • Bayer
Investigators  ICMJE
Principal Investigator: Stuart Connolly, MD Population Health Research Institute
PRS Account Population Health Research Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP