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PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban

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ClinicalTrials.gov Identifier: NCT04142658
Recruitment Status : Recruiting
First Posted : October 29, 2019
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
CryoLife, Inc.

Tracking Information
First Submitted Date  ICMJE October 9, 2019
First Posted Date  ICMJE October 29, 2019
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE May 1, 2020
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • Co-Primary Efficacy Objective [ Time Frame: 2 years ]
    To determine if apixaban is non-inferior to warfarin (INR target range 2.0 - 3.0) for patients with an On-X mechanical heart valve implanted in the aortic position for the primary composite outcome of valve thrombosis and valve-related thromboembolism.
  • Co-Primary Efficacy Objective [ Time Frame: 2 years ]
    To determine if apixaban provides acceptable anticoagulation for patients with an On-X mechanical heart valve implanted in the aortic position for the primary composite outcome of valve thrombosis and valve-related thromboembolism compared with an objective performance criterion.
  • Number of major bleeding events (superiority) [ Time Frame: 2 years ]
    To determine if apixaban is superior to warfarin (INR target range 2.0 - 3.0) in the safety outcome of major bleeding in patients with an On-X mechanical heart valve implanted in the aortic position.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
  • Number of valve-related thrombotic events (non-inferiority) [ Time Frame: 2 years ]
    To determine if apixaban is non-inferior to warfarin (INR target range 2.0-3.0) for patients with an On-X mechanical heart valve implanted in the aortic position for the primary composite outcome of valve thrombosis
  • Number of major bleeding events (superiority) [ Time Frame: 2 years ]
    To determine if apixaban is superior to warfarin (INR target range 2.0 - 3.0) in the safety outcome of major bleeding in patients with an On-X mechanical heart valve implanted in the aortic position
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • Number of valve-related thrombotic events (superiority) [ Time Frame: 2 years ]
    To determine if apixaban is superior to warfarin (INR target range 2.0 - 3.0) for the primary composite outcome of valve thrombosis and valve-related thromboembolism in patients with an On-X mechanical heart valve implanted in the aortic position.
  • Secondary Efficacy Objective [ Time Frame: 2 years ]
    To compare apixaban with warfarin (INR target range 2.0 - 3.0) for the individual components of the primary outcome (valve thrombosis and valve-related thromboembolism) in patients with an On-X mechanical heart valve implanted in the aortic position.
  • Secondary Efficacy Objective [ Time Frame: 2 years ]
    To compare apixaban with warfarin (INR target range 2.0 - 3.0) for the primary composite outcome of valve thrombosis and valve-related thromboembolism in prespecified subgroups of patients with an On-X mechanical heart valve implanted in the aortic position.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
Number of valve-related thrombotic events (superiority) [ Time Frame: 2 years ]
To determine if apixaban is superior to warfarin (INR target range 2.0 - 3.0) in the primary composite outcome of valve thrombosis in participants with an On-X mechanical heart valve
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban
Official Title  ICMJE A Prospective, Randomized, Active (Warfarin) Controlled, Parallel-arm Clinical Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely and Effectively on Apixaban
Brief Summary Currently, warfarin is the only approved anticoagulation for patients with mechanical valves. The purpose of this study is to determine if participants with an On-X Prosthetic Heart Valve / On-X aortic valve can be maintained safely and effectively on apixaban. Both the On-X aortic valve and apixaban have been approved for use by the US Food and Drug Administration (FDA) but they have not been approved to be used together.
Detailed Description There is an unmet clinical need for an alternative to warfarin, such as a direct oral anticoagulant (DOAC), as anticoagulation in participants with an aortic mechanical prosthetic valve. Some participants may be genetically hyper- or hypo-responsive to warfarin, which makes management difficult. Another small group of participants is allergic to warfarin. A much larger group of participants has difficulty maintaining warfarin control due to dietary and drug interactions. Finally, the requirement for routine blood testing makes people reluctant to take warfarin. All of these factors drive younger participants in need of aortic valve replacement (AVR) toward selection of a tissue valve instead of a mechanical valve. Despite multiple studies (randomized, matched and risk adjusted) that show that tissue valves are associated with worse outcomes, younger participants choose this type of valve to avoid warfarin. In addition, multiple clinical studies have shown valve reoperation rates are higher for tissue valves used in these younger participants. Providing an alternative to warfarin anticoagulation may lead younger participants to choose a mechanical valve with greater durability and better clinical outcomes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel control and treatment arm at a 1:1 ratio.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Aortic Valve Disease
  • Aortic Valve Stenosis
  • Aortic Valve Failure
Intervention  ICMJE
  • Drug: Apixaban 5 MG

    For patients that do NOT meet the following criteria

    • age ≥ 80 years
    • weight ≤ 60 kilograms
    • creatinine ≥ 1.5 mg/dL (133 micromol/L)
  • Drug: Apixaban 2.5 MG

    For patients that meet at least 2 of the following criteria

    • age ≥ 80 years
    • weight ≤ 60 kilograms
    • creatinine ≥ 1.5 mg/dL (133 micromol/L)
  • Drug: Warfarin
    Active Control Intervention
  • Device: On-X Aortic Mechanical Valve
    Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Study Arms  ICMJE
  • Experimental: Apixaban
    Apixaban 5 mg twice daily(BID) or 2.5 mg BID
    Interventions:
    • Drug: Apixaban 5 MG
    • Drug: Apixaban 2.5 MG
    • Device: On-X Aortic Mechanical Valve
  • Active Comparator: Warfarin
    Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)
    Interventions:
    • Drug: Warfarin
    • Device: On-X Aortic Mechanical Valve
Publications *

*   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: January 3, 2020)
1000
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2019)
1186
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female at least 18 years of age at the time of giving informed consent.
  • Participants currently receiving warfarin anticoagulation and who are able to receive warfarin with a target INR 2.0 to 3.0.
  • Participants are able to take low-dose aspirin at a dose of 75 -100 mg daily or have a documented contraindication to aspirin use.
  • Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
  • Female participants of childbearing potential, including those who are less than 2 years post-menopausal, must agree to, and comply with using a highly effective method of birth control (eg, barrier contraceptives [condom or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices or sexual abstinence) while partaking in this study. In addition, all women of childbearing potential must agree to continue to use birth control throughout the study until last study visit.
  • Informed of the full nature and purpose of the study, including possible risks and side effects, given ample time and opportunity to read and understand this information, and sign and date the written informed consent before inclusion in the study.

Exclusion Criteria:

  • Mechanical valve in any position other than aortic valve.
  • Any cardiac surgery in the three months (90 days) prior to enrollment.
  • Need to be on aspirin >100 mg daily or a P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel, or ticlopidine).
  • Known hypersensitivity or other contraindication to apixaban.
  • On dialysis or a creatinine clearance < 25 mL/min.
  • Ischemic stroke or intracranial hemorrhage within 3 months.
  • Active pathological bleeding at the time of screening for enrollment.
  • Active endocarditis at the time of screening for enrollment.
  • Pregnant, plan to become pregnant, or are breast feeding.
  • On concomitant combined strong P-gp and CYP3A4 inducers or inhibitors.
  • History of non-compliance with recommended monthly INR testing.
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: Brittanny Boyer, BS 1-888-427-9654 proactxainfo@cryolife.com
Contact: Amy Mahoney, BS proactxainfo@cryolife.com
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT04142658
Other Study ID Numbers  ICMJE ONX1801.000-C
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CryoLife, Inc.
Study Sponsor  ICMJE CryoLife, Inc.
Collaborators  ICMJE Duke Clinical Research Institute
Investigators  ICMJE
Study Chair: Lars Svensson, MD, PhD Steering Committee
Study Chair: John Alexander, MD Steering Committee
PRS Account CryoLife, Inc.
Verification Date September 2021

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