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

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ClinicalTrials.gov Identifier: NCT04142658
Recruitment Status : Not yet recruiting
First Posted : October 29, 2019
Last Update Posted : November 1, 2019
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
CryoLife, 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.

Condition or disease Intervention/treatment Phase
Aortic Valve Disease Aortic Valve Stenosis Aortic Valve Failure Drug: Apixaban 5 MG Drug: Apixaban 2.5 MG Drug: Warfarin Device: On-X Aortic Mechanical Valve Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel control and treatment arm at a 1:1 ratio.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Apixaban

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

For participants randomized to apixaban, INR testing will be performed on the current warfarin dose with the following algorithm to initiate apixaban

  • INR < 2; stop warfarin and start apixaban
  • INR 2.0 to 3.0; hold warfarin for 2 days, start apixaban on day 3
  • INR > 3.0 to 4.0; hold warfarin for 4 days, start apixaban on day 5
  • INR > 4.0; hold warfarin for 2 days, recheck INR, refer to steps 1, 2, or 3
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.

Active Comparator: Warfarin
Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0)
Drug: Warfarin
Active Control Intervention

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.




Primary Outcome Measures :
  1. Number of valve-related thrombotic events (non-inferiority) [ Time Frame: 2 years ]
    To determine if apixaban is non-inferior to warfarin (INR target range 2.0-3.0) for patients with an On-X mechanical heart valve implanted in the aortic position for the primary composite outcome of valve thrombosis

  2. Number of major bleeding events (superiority) [ Time Frame: 2 years ]
    To determine if apixaban is superior to warfarin (INR target range 2.0 - 3.0) in the safety outcome of major bleeding in patients with an On-X mechanical heart valve implanted in the aortic position


Secondary Outcome Measures :
  1. 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) in the primary composite outcome of valve thrombosis in participants with an On-X mechanical heart valve



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • Needs 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04142658


Contacts
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Contact: Brittanny Boyer, BS 678-290-4386 boyer.brittanny@cryolife.com
Contact: Amy Mahoney, BS 678-290-4596 mahoney.amy@cryolife.com

Locations
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United States, Florida
St. Vincent's Medical Center Not yet recruiting
Jacksonville, Florida, United States, 32204
Contact: Jessie Hamner, MSN RN    904-308-5764    jessica.hamner@ascension.org   
Principal Investigator: Mark Mostovych, MD         
United States, Minnesota
St. Mary's Hospital/ Mayo Foundation Not yet recruiting
Rochester, Minnesota, United States, 55902
Contact: Janell Keehn, BS    507-255-8605    Keehn.Janell@mayo.edu   
Principal Investigator: Alberto Pochettino, MD         
United States, Nebraska
University of Nebraska Medical Center Not yet recruiting
Omaha, Nebraska, United States, 68198
Contact: Natalia Mccain, RN BSN    402-559-3213    natalia.mccain@unmc.edu   
Principal Investigator: Aleem Siddique, MD         
United States, Pennsylvania
Lehigh Valley Hospital Allentown Not yet recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Deborah Herr, RN, MSN    610-402-7195    Deborah.Herr@lvhn.org   
Principal Investigator: James Wu, MD         
United States, Texas
The Heart Hospital at Baylor Plano Not yet recruiting
Plano, Texas, United States, 75093
Contact: Megan White, MS    469-814-4181    Megan.white1@BSWHealth.org   
Principal Investigator: Katherine Harrington, MD         
Sponsors and Collaborators
CryoLife, Inc.
Duke Clinical Research Institute
Investigators
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Study Chair: Lars Svensson, MD, PhD Steering Committee
Study Chair: John Alexander, MD Steering Committee

Publications:

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Responsible Party: CryoLife, Inc.
ClinicalTrials.gov Identifier: NCT04142658     History of Changes
Other Study ID Numbers: ONX1801.000-C
First Posted: October 29, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Warfarin
Apixaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action