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

March 18, 2024 updated by: Artivion Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

863

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85712
        • Tucson Heart Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • CHI St. Vincent Heart Institute
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Palo Alto, California, United States, 94305
        • Stanford University Medical Center
      • San Diego, California, United States, 92123
        • Sharp Memorial
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • New Haven, Connecticut, United States, 06510
        • Yale- New Haven Hospital
    • Florida
      • Clearwater, Florida, United States, 33756
        • Baycare Health / Morton Plant Hospital
      • Gainesville, Florida, United States, 32608
        • Shands Hospital (University of Florida Health)
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Tallahassee, Florida, United States, 32308
        • Tallahassee Research Institute
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, United States, 30332
        • Emory University Hospital
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center
      • Marietta, Georgia, United States, 30060
        • Wellstar Kennestone Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Rockford, Illinois, United States, 61107
        • OSF Cardiovascular Institute
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Franciscan Health Indianapolis
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health Methodist Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • John's Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Abbott Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55422
        • University of Minnesota
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic Rochester
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63105
        • Washington University Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai- St. Luke's Hospital
      • New York, New York, United States, 10065
        • NewYork-Presbyterian Hospital
      • New York, New York, United States, 10065
        • NewYork-Presbyterian/ Weill Cornell Medical Center
      • Poughkeepsie, New York, United States, 12601
        • Vassar Brothers Medical Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Atrium Health Carolinas Medical Center (CMC)
      • Durham, North Carolina, United States, 27708
        • Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73120
        • Oklahoma Heart Hospital
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital Allentown
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Health Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Shadyside
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57108
        • Avera Health / North Central Heart
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tristar Centennial Medical Center
    • Texas
      • Dallas, Texas, United States, 75235
        • William P. Clements Jr. University Hospital
      • Fort Worth, Texas, United States, 76107
        • TCU School of Medicine
      • Houston, Texas, United States, 77030
        • The University of Texas Health Science Center at Houston
      • Plano, Texas, United States, 75093
        • The Heart Hospital at Baylor Plano
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Hospital
    • Virginia
      • Richmond, Virginia, United States, 23229
        • Henrico Doctors' Hospital
      • Roanoke, Virginia, United States, 24014
        • Carilion Roanoke Memorial Hospital
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center
      • Tacoma, Washington, United States, 98405
        • Tacoma General Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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)
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 Names:
  • On-X Ascending Aortic Prosthesis (AAP)
Drug: Warfarin
Active Control Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of Valve Thrombosis and Valve-related Thromboembolism
Time Frame: through study closure, a median follow-up of 13.5 months
Valve thrombosis was defined as any thrombus, not caused by infection, attached to or near an implanted On-X valve that occluded part of the blood-flow path, interfered with valve function, or was sufficiently large to warrant treatment other than continued oral anticoagulation. Valve-related thromboembolism was defined as any thromboembolic stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism to an organ or limb that was not associated with infection or an intracardiac tumor and was definitely or possibly related to the valve.
through study closure, a median follow-up of 13.5 months
Major Bleeding
Time Frame: through study closure, a median follow-up of 13.5 months
Major bleeding defined as any episode of internal or external bleeding that caused death, hospitalization, or permanent injury or necessitated transfusion, pericardiocentesis, or reoperation.
through study closure, a median follow-up of 13.5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years
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.
2 years
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.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Artivion Inc.

Collaborators

Duke Clinical Research Institute

Investigators

  • Study Chair: Lars Svensson, MD, PhD, Steering Committee
  • Study Chair: John Alexander, MD, Steering Committee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2020

Primary Completion (Actual)

December 12, 2022

Study Completion (Actual)

December 12, 2022

Study Registration Dates

First Submitted

October 9, 2019

First Submitted That Met QC Criteria

October 25, 2019

First Posted (Actual)

October 29, 2019

Study Record Updates

Last Update Posted (Actual)

March 20, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONX1801.000-C

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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