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Trial record 1 of 1 for:    PROACT Xa
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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 : Terminated (Safety)
First Posted : October 29, 2019
Last Update Posted : May 17, 2023
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
Artivion Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Aortic Valve Disease Aortic Valve Stenosis Aortic Valve Failure Drug: Apixaban 5 MG Drug: Apixaban 2.5 MG Drug: Warfarin Device: On-X Aortic Mechanical Valve Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 863 participants
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
Official Title: 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
Actual Study Start Date : May 1, 2020
Actual Primary Completion Date : December 12, 2022
Actual Study Completion Date : December 12, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arms and Interventions
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Arm Intervention/treatment
Experimental: Apixaban
Apixaban 5 mg twice daily(BID) or 2.5 mg BID
 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)

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.
Other Name: On-X Ascending Aortic Prosthesis (AAP)
Active Comparator: Warfarin
Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)
 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.
Other Name: On-X Ascending Aortic Prosthesis (AAP)


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


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

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.
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT04142658


Locations
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Sponsors and Collaborators
Artivion Inc.
Duke Clinical Research Institute
Investigators
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Study Chair: Lars Svensson, MD, PhD Steering Committee
Study Chair: John Alexander, MD Steering Committee
More Information
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Publications:

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Responsible Party: Artivion Inc.
ClinicalTrials.gov Identifier: NCT04142658    
Other Study ID Numbers: ONX1801.000-C
First Posted: October 29, 2019    Key Record Dates
Last Update Posted: May 17, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Factor Xa Inhibitors
Aortic Valve Stenosis
Aortic Valve Disease
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Warfarin
 Apixaban
Anticoagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action