Clinical trial NCT00291525: Randomized On-X Anticoagulation Trial
Official title: Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Valve Disease
Keywords: valve
prosthesis
antithrombotics
randomized
Lead sponsor: On-X Life Technologies, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Clinipace Worldwide
name: Acelis Connected Health
name: WCG IRB
name: Avania
First posted: 2006-02-14
Enrollment: 977
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Various patient groups with the On-X Valve can be maintained safely on lower doses of blood thinner(Coumadin®) or on antiplatelet drugs (aspirin/Plavix®) only rather than the standard dose of Coumadin and aspirin presently recommended by ACC/AHA or ACCP professional societies.

Detailed description: This is a longitudinal, randomized (randomization to occur at the 3-month follow-up) study comparing the On-X valve on low dose anticoagulation (test group) to concomitant control groups of On-X valves receiving standard Coumadin/aspirin therapy, and also to FDA objective performance criteria (OPC) for heart valve replacement. It is a multicenter study consisting of up to 50 centers in the United States, Canada, and Italy enrolling and randomizing no more than 1200 patients (200 in each of 6 groups). There are three test arms of the study: low risk aortic valve replacement, high risk aortic valve replacement, and mitral valve replacement. Each arm has an equivalent control. Test therapies are: low risk aortic valve replacement - aspirin/Plavix, high risk aortic valve replacement - Coumadin at INR of 1.5 to 2.0 plus aspirin, and mitral valve replacement - Coumadin at an INR of 2.0 to 2.5 plus aspirin. Follow-up will run for up to 8 years in each patient. Each arm is independent and the low risk aortic and high risk aortic arms are completed. The low risk aortic arm was closed early resulting in a reduction of the estimated total enrollment with randomization to 1000. The high risk arm is completed with FDA review and this arm had 375 randomized enrollees. The mitral arm continues to enroll with a planned randomized enrollment of 400.

Eligibility criteria: Inclusion Criteria:

* Patients requiring isolated aortic valve replacement (AVR), or isolated mitral valve replacement (MVR).
* AVR patients receiving low dose or antiplatelet only anticoagulation will be divided into groups at low risk and high risk for thromboembolism with all patients being in the low risk group except for patients with the following conditions which place a patient in the high risk group:

  * Chronic atrial fibrillation
  * Left ventricular ejection fraction \< 30 %
  * Enlarged left atrium \>50mm diameter
  * Spontaneous echo contrasts in the left atrium
  * Vascular pathology
  * Neurological events
  * Hypercoagulability
  * Left or right ventricular aneurysm
  * Lack of platelet response to aspirin or clopidogrel
  * Women receiving estrogen replacement therapy
* Concomitant cardiac surgery is allowed
* Adult patients

Exclusion Criteria:

* Right side valve replacement
* Double (aortic plus mitral) valve replacement
* Patients with active endocarditis at the time of implant
* Previous confirmed or suspected thromboembolic event or thrombophlebitis
* Other terminal illness
* Patients who are in an emergency state
* Inability to return for required follow-ups
* Patients with an On-X valve implanted within the study and subsequently explanted
* Patients who are known to be pregnant, plan to become pregnant or are lactating
* Patients with acquired immunodeficiency syndrome or know to be HIV positive
* Patients who are prison inmates or known drug or alcohol abusers
* Patients unable to give adequate informed consent.

Primary outcomes:
measure: Thromboembolism
timeFrame: 8 years
measure: Valve Thrombosis
timeFrame: 8 years
measure: Bleeding Events
timeFrame: 8 years
Secondary outcomes:
measure: Valve-Related Mortality
timeFrame: 8 years
measure: Valve Hemodynamics
timeFrame: 5 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Medical Center
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Newark
country: United States
facility: Christiana Health Care Services
state: Delaware
city: Washington
country: United States
facility: Medstar Heart & Vascular Institute
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital - University of Florida
state: Florida
city: Kissimmee
country: United States
facility: Cardiac Surgical Associates
state: Florida
city: Miami
country: United States
facility: South Florida Heart & Lung
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: St. Francis Heart Center
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Brigham & 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: St. Joseph Mercy Hospital
state: Michigan
city: Kansas City
country: United States
facility: Mid America Heart institute
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital - Washington University
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: New York
country: United States
facility: St. Luke's Roosevelt
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Raleigh
country: United States
facility: WakeMed
state: North Carolina
city: Raleigh
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital - Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma/VA Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart & Vascular Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Lubbock
country: United States
facility: Texas Cardiac Center
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White - Plano
state: Texas
city: Fredericksburg
country: United States
facility: Mary Washington Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: St. Luke's Aurora Health Care
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Quebec City
country: Canada
facility: IUCPQ Chirurgie Cardiaque
state: Quebec
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: John Puskas, MD
role: STUDY_DIRECTOR
References:
citation: Puskas JD; PROACT Investigators. Reply: Low-Thrombogenicity Mechanical Heart Valves: Which Antithrombotic Strategy? J Am Coll Cardiol. 2018 Oct 9;72(15):1879-1880. doi: 10.1016/j.jacc.2018.07.063. No abstract available.
citation: 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.
citation: Yanagawa B, Levitsky S, Puskas JD; PROACT Investigators. Reduced anticoagulation is safe in high-risk patients with the On-X mechanical aortic valve. Curr Opin Cardiol. 2015 Mar;30(2):140-145. doi: 10.1097/HCO.0000000000000149.
citation: Puskas JD, Gerdisch M, Nichols D, Fermin L, Rhenman B, Kapoor D, Copeland J, Quinn R, Hughes GC, Azar H, McGrath M, Wait M, Kong B, Martin T, Douville EC, Meyer S, Ye J, Jamieson WRE, Landvater L, Hagberg R, Trotter T, Armitage J, Askew J, Accola K, Levy P, Duncan D, Yanagawa B, Ely J, Graeve A; PROACT Investigators. Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement. J Am Coll Cardiol. 2018 Jun 19;71(24):2717-2726. doi: 10.1016/j.jacc.2018.03.535.
citation: Chu MWA, Ruel M, Graeve A, Gerdisch MW, Damiano RJ Jr, Smith RL 2nd, Keeling WB, Wait MA, Hagberg RC, Quinn RD, Sethi GK, Floridia R, Barreiro CJ, Pruitt AL, Accola KD, Dagenais F, Markowitz AH, Ye J, Sekela ME, Tsuda RY, Duncan DA, Swistel DG, Harville LE 3rd, DeRose JJ, Lehr EJ, Puskas JD; PROACT Mitral Investigators. WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial. Ann Thorac Surg. 2022 Jan 28:S0003-4975(22)00138-2. doi: 10.1016/j.athoracsur.2022.01.015. Online ahead of print.