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

NCT ID: NCT04142658

Last Updated: 2024-03-20

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

863 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-01

Study Completion Date

2022-12-12

Brief Summary

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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

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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.

Conditions

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Aortic Valve Disease Aortic Valve Stenosis Aortic Valve Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel control and treatment arm at a 1:1 ratio.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Apixaban

Apixaban 5 mg twice daily(BID) or 2.5 mg BID

Group Type EXPERIMENTAL

Apixaban 5 MG

Intervention Type DRUG

For patients that do NOT meet the following criteria

* age ≥ 80 years
* weight ≤ 60 kilograms
* creatinine ≥ 1.5 mg/dL (133 micromol/L)

Apixaban 2.5 MG

Intervention Type DRUG

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)

On-X Aortic Mechanical Valve

Intervention Type DEVICE

Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.

Warfarin

Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

Active Control Intervention

On-X Aortic Mechanical Valve

Intervention Type DEVICE

Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.

Interventions

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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)

Intervention Type 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)

Intervention Type DRUG

Warfarin

Active Control Intervention

Intervention Type DRUG

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.

Intervention Type DEVICE

Other Intervention Names

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On-X Ascending Aortic Prosthesis (AAP)

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke Clinical Research Institute

OTHER

Sponsor Role collaborator

Artivion Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lars Svensson, MD, PhD

Role: STUDY_CHAIR

Steering Committee

John Alexander, MD

Role: STUDY_CHAIR

Steering Committee

Locations

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Tucson Heart Center

Tucson, Arizona, United States

Site Status

CHI St. Vincent Heart Institute

Little Rock, Arkansas, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Sharp Memorial

San Diego, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Yale- New Haven Hospital

New Haven, Connecticut, United States

Site Status

Baycare Health / Morton Plant Hospital

Clearwater, Florida, United States

Site Status

Shands Hospital (University of Florida Health)

Gainesville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Tallahassee Research Institute

Tallahassee, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Site Status

Wellstar Kennestone Hospital

Marietta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

OSF Cardiovascular Institute

Rockford, Illinois, United States

Site Status

Indiana University Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Franciscan Health Indianapolis

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

John's Hopkins University

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health

Ann Arbor, Michigan, United States

Site Status

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

Saint Luke's Hospital

Kansas City, Missouri, United States

Site Status

Washington University Medical Center

St Louis, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Mount Sinai- St. Luke's Hospital

New York, New York, United States

Site Status

NewYork-Presbyterian Hospital

New York, New York, United States

Site Status

NewYork-Presbyterian/ Weill Cornell Medical Center

New York, New York, United States

Site Status

Vassar Brothers Medical Center

Poughkeepsie, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Atrium Health Carolinas Medical Center (CMC)

Charlotte, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

ProMedica Toledo Hospital

Toledo, Ohio, United States

Site Status

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Hospital Allentown

Allentown, Pennsylvania, United States

Site Status

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

UPMC Shadyside

Pittsburgh, Pennsylvania, United States

Site Status

Avera Health / North Central Heart

Sioux Falls, South Dakota, United States

Site Status

Tristar Centennial Medical Center

Nashville, Tennessee, United States

Site Status

William P. Clements Jr. University Hospital

Dallas, Texas, United States

Site Status

TCU School of Medicine

Fort Worth, Texas, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

The Heart Hospital at Baylor Plano

Plano, Texas, United States

Site Status

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status

Henrico Doctors' Hospital

Richmond, Virginia, United States

Site Status

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Tacoma General Hospital

Tacoma, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Wauwatosa, Wisconsin, United States

Site Status

Countries

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United States

References

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McNicholas KW, Ivey TD, Metras J, Szentpetery S, Marra SW, Masters RG, Dilling EW, Slaughter MS, Mack MJ. North American multicenter experience with the On-X prosthetic heart valve. J Heart Valve Dis. 2006 Jan;15(1):73-8; discussion 79.

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Palatianos GM, Laczkovics AM, Simon P, Pomar JL, Birnbaum DE, Greve HH, Haverich A. Multicentered European study on safety and effectiveness of the On-X prosthetic heart valve: intermediate follow-up. Ann Thorac Surg. 2007 Jan;83(1):40-6. doi: 10.1016/j.athoracsur.2006.08.010.

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Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12.

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Jawitz OK, Wang TY, Lopes RD, Chavez A, Boyer B, Kim H, Anstrom KJ, Becker RC, Blackstone E, Ruel M, Thourani VH, Puskas JD, Gerdisch MW, Johnston D, Capps S, Alexander JH, Svensson LG. Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve. Am Heart J. 2020 Sep;227:91-99. doi: 10.1016/j.ahj.2020.06.014. Epub 2020 Jun 25.

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Reference Type DERIVED
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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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ONX1801.000-C

Identifier Type: -

Identifier Source: org_study_id

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