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

Phase 3

Terminated

Conditions: Aortic Valve Disease
Aortic Valve Stenosis
Aortic Valve Failure

Interventions: Drug: Warfarin
Drug: Apixaban 5 MG
Drug: Apixaban 2.5 MG
Device: On-X Aortic Mechanical Valve

Registration Number: NCT04142658

Lead Sponsor: Artivion Inc.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 863

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Warfarin	Warfarin	Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)
Apixaban	On-X Aortic Mechanical Valve	Apixaban 5 mg twice daily(BID) or 2.5 mg BID
Apixaban	Apixaban 5 MG	Apixaban 5 mg twice daily(BID) or 2.5 mg BID
Apixaban	Apixaban 2.5 MG	Apixaban 5 mg twice daily(BID) or 2.5 mg BID
Warfarin	On-X Aortic Mechanical Valve	Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)

Primary Outcome Measures

Name	Time	Method
Major Bleeding	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.
Composite of Valve Thrombosis and Valve-related Thromboembolism	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (62): Stanford University Medical Center
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Palo Alto, California, United States
Piedmont Atlanta Hospital
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Atlanta, Georgia, United States
Northwestern Memorial Hospital
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Chicago, Illinois, United States
John's Hopkins University
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Baltimore, Maryland, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
UPMC Shadyside
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Pittsburgh, Pennsylvania, United States
Brigham and Women's Hospital
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Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Cleveland Clinic
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Cleveland, Ohio, United States
The University of Texas Health Science Center at Houston
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Houston, Texas, United States
University of Washington Medical Center
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Seattle, Washington, United States
Sharp Memorial
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San Diego, California, United States
Indiana University Health Methodist Hospital
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Indianapolis, Indiana, United States
Franciscan Health Indianapolis
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Indianapolis, Indiana, United States
Abbott Northwestern Hospital
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Minneapolis, Minnesota, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Mayo Clinic Rochester
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Rochester, Minnesota, United States
University of Nebraska Medical Center
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Omaha, Nebraska, United States
Duke University
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Durham, North Carolina, United States
Oklahoma Heart Hospital
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Oklahoma City, Oklahoma, United States
Tristar Centennial Medical Center
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Nashville, Tennessee, United States
University of Utah Hospital
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Salt Lake City, Utah, United States
University of South Florida
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Tampa, Florida, United States
Tucson Heart Center
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Tucson, Arizona, United States
CHI St. Vincent Heart Institute
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Little Rock, Arkansas, United States
Loma Linda University Medical Center
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Loma Linda, California, United States
Hartford Hospital
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Hartford, Connecticut, United States
Baycare Health / Morton Plant Hospital
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Clearwater, Florida, United States
Tallahassee Research Institute
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Tallahassee, Florida, United States
Northeast Georgia Medical Center
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Gainesville, Georgia, United States
Emory University Hospital
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Atlanta, Georgia, United States
Wellstar Kennestone Hospital
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Marietta, Georgia, United States
OSF Cardiovascular Institute
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Rockford, Illinois, United States
University of Iowa
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Iowa City, Iowa, United States
Missouri Baptist Medical Center
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Saint Louis, Missouri, United States
Washington University Medical Center
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Saint Louis, Missouri, United States
Mount Sinai- St. Luke's Hospital
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New York, New York, United States
NewYork-Presbyterian Hospital
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New York, New York, United States
Vassar Brothers Medical Center
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Poughkeepsie, New York, United States
NewYork-Presbyterian/ Weill Cornell Medical Center
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New York, New York, United States
University of Rochester Medical Center
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Rochester, New York, United States
Atrium Health Carolinas Medical Center (CMC)
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Charlotte, North Carolina, United States
ProMedica Toledo Hospital
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Toledo, Ohio, United States
Avera Health / North Central Heart
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Sioux Falls, South Dakota, United States
William P. Clements Jr. University Hospital
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Dallas, Texas, United States
The Heart Hospital at Baylor Plano
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Plano, Texas, United States
Swedish Medical Center
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Seattle, Washington, United States
Carilion Roanoke Memorial Hospital
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Roanoke, Virginia, United States
Tacoma General Hospital
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Tacoma, Washington, United States
Medical College of Wisconsin
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Wauwatosa, Wisconsin, United States
TCU School of Medicine
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Fort Worth, Texas, United States
Maine Medical Center
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Portland, Maine, United States
Lehigh Valley Hospital Allentown
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Allentown, Pennsylvania, United States
Penn State Health Milton S. Hershey Medical Center
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Hershey, Pennsylvania, United States
Shands Hospital (University of Florida Health)
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Gainesville, Florida, United States
University of Michigan Health
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Ann Arbor, Michigan, United States
Yale- New Haven Hospital
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New Haven, Connecticut, United States
AdventHealth Orlando
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Orlando, Florida, United States
Saint Luke's Hospital
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Kansas City, Missouri, United States
Henrico Doctors' Hospital
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Richmond, Virginia, United States
University of Wisconsin
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Madison, Wisconsin, United States
Thomas Jefferson University
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Philadelphia, Pennsylvania, United States