Clinical trial NCT04142658: PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Aortic Valve Disease
Aortic Valve Stenosis
Aortic Valve Failure
Lead sponsor: Artivion Inc.
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
First posted: 2019-10-29
Enrollment: 863
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel control and treatment arm at a 1:1 ratio.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Composite of Valve Thrombosis and Valve-related Thromboembolism
timeFrame: through study closure, a median follow-up of 13.5 months
measure: Major Bleeding
timeFrame: through study closure, a median follow-up of 13.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Heart Center
state: Arizona
city: Little Rock
country: United States
facility: CHI St. Vincent Heart Institute
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale- New Haven Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Baycare Health / Morton Plant Hospital
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital (University of Florida Health)
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Rockford
country: United States
facility: OSF Cardiovascular Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Health Indianapolis
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: John's Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Mount Sinai- St. Luke's Hospital
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian/ Weill Cornell Medical Center
state: New York
city: Poughkeepsie
country: United States
facility: Vassar Brothers Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Carolinas Medical Center (CMC)
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital Allentown
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Health / North Central Heart
state: South Dakota
city: Nashville
country: United States
facility: Tristar Centennial Medical Center
state: Tennessee
city: Dallas
country: United States
facility: William P. Clements Jr. University Hospital
state: Texas
city: Fort Worth
country: United States
facility: TCU School of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Plano
country: United States
facility: The Heart Hospital at Baylor Plano
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Richmond
country: United States
facility: Henrico Doctors' Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Tacoma General Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Wauwatosa
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Steering Committee
name: Lars Svensson, MD, PhD
role: STUDY_CHAIR
affiliation: Steering Committee
name: John Alexander, MD
role: STUDY_CHAIR
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