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

NCT04142658 | Terminated Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: ONX1801.000-C
• Study Type: interventional
• Target: 863
• Locations: 1 country
• Sites: 62

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.

Conditions

Aortic Valve Disease; Aortic Valve Stenosis; Aortic Valve Failure

Outcome Measures

Primary Outcomes (2)

• Composite of Valve Thrombosis and Valve-related Thromboembolism

  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

  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

Study Arms (2)

Apixaban

EXPERIMENTAL

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

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

Warfarin

ACTIVE COMPARATOR

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

Drug: Warfarin; Device: On-X Aortic Mechanical Valve

Interventions

Apixaban 5 MG 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

Apixaban 2.5 MG 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)

Apixaban

Warfarin DRUG

Active Control Intervention

Warfarin

On-X Aortic Mechanical Valve DEVICE

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

Also known as: On-X Ascending Aortic Prosthesis (AAP)

Apixaban; Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Artivion Inc.: lead
• Duke Clinical Research Institute: collaborator

Study Sites (62)

Tucson Heart Center

Tucson, Arizona, 85712, United States

Location

CHI St. Vincent Heart Institute

Little Rock, Arkansas, 72205, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Sharp Memorial

San Diego, California, 92123, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Yale- New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Baycare Health / Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

Shands Hospital (University of Florida Health)

Gainesville, Florida, 32608, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital

Atlanta, Georgia, 30332, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Wellstar Kennestone Hospital

Marietta, Georgia, 30060, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

OSF Cardiovascular Institute

Rockford, Illinois, 61107, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Franciscan Health Indianapolis

Indianapolis, Indiana, 46237, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

John's Hopkins University

Baltimore, Maryland, 21218, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health

Ann Arbor, Michigan, 48109, United States

Location

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55422, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

Washington University Medical Center

St Louis, Missouri, 63105, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Mount Sinai- St. Luke's Hospital

New York, New York, 10029, United States

Location

NewYork-Presbyterian Hospital

New York, New York, 10065, United States

Location

NewYork-Presbyterian/ Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Vassar Brothers Medical Center

Poughkeepsie, New York, 12601, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Atrium Health Carolinas Medical Center (CMC)

Charlotte, North Carolina, 28203, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

ProMedica Toledo Hospital

Toledo, Ohio, 43606, United States

Location

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, 73120, United States

Location

Lehigh Valley Hospital Allentown

Allentown, Pennsylvania, 18103, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

Avera Health / North Central Heart

Sioux Falls, South Dakota, 57108, United States

Location

Tristar Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

William P. Clements Jr. University Hospital

Dallas, Texas, 75235, United States

Location

TCU School of Medicine

Fort Worth, Texas, 76107, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

The Heart Hospital at Baylor Plano

Plano, Texas, 75093, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Henrico Doctors' Hospital

Richmond, Virginia, 23229, United States

Location

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, 24014, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

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MeSH Terms

Conditions

Aortic Valve Disease; Aortic Valve Stenosis

Interventions

apixaban; Warfarin

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Melissa Thalin, Director, New Indications
• Organization: Artivion

melissa.thalin@artivion.com

770-419-3355

Study Officials

• Lars Svensson, MD, PhD

  Steering Committee

  STUDY CHAIR

• John Alexander, MD

  Steering Committee

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel control and treatment arm at a 1:1 ratio.

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 29, 2019
• Study Start: May 1, 2020
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: March 20, 2024
• Results First Posted: March 20, 2024

Record last verified: 2024-03

Locations

US (62)