Randomized On-X Anticoagulation Trial

Heart Valve Disease Clinical Trial

— PROACT  

Official title:

Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00291525
• Other study ID #: 2005-01
• Secondary ID: G050208
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 6, 2006
• Est. completion date: December 31, 2022

Study information

• Verified date: September 2022
• Source: On-X Life Technologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Valve Disease
• Heart Valve Diseases

Intervention

Device:
• On-X valve using reduced anticoagulation
Valve replacement with antiplatelet agents or lowered warfarin
• On-X Valve with Standard warfarin Therapy
Valve replacement with standard dosage warfarin

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Science Centre	London	Ontario
Canada	Ottawa Heart Institute	Ottawa	Ontario
Canada	IUCPQ Chirurgie Cardiaque	Quebec City	Quebec
Canada	University of British Columbia	Vancouver	British Columbia
United States	New Mexico Heart Institute	Albuquerque	New Mexico
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospital - Cleveland	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Mary Washington Hospital	Fredericksburg	Virginia
United States	Shands Hospital - University of Florida	Gainesville	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Texas Heart Institute	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	St. Francis Heart Center	Indianapolis	Indiana
United States	Mid America Heart institute	Kansas City	Missouri
United States	Cardiac Surgical Associates	Kissimmee	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Loma Linda University	Loma Linda	California
United States	Texas Cardiac Center	Lubbock	Texas
United States	South Florida Heart & Lung	Miami	Florida
United States	St. Luke's Aurora Health Care	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Montefiore Medical Center	New York	New York
United States	St. Luke's Roosevelt	New York	New York
United States	Christiana Health Care Services	Newark	Delaware
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	University of Oklahoma/VA Oklahoma City	Oklahoma City	Oklahoma
United States	Florida Hospital	Orlando	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Baylor Scott & White - Plano	Plano	Texas
United States	Maine Medical Center	Portland	Maine
United States	Providence Heart & Vascular Institute	Portland	Oregon
United States	Duke University Medical Center	Raleigh	North Carolina
United States	WakeMed	Raleigh	North Carolina
United States	Barnes Jewish Hospital - Washington University	Saint Louis	Missouri
United States	Swedish Medical Center	Seattle	Washington
United States	MultiCare Health System	Tacoma	Washington
United States	Cotton-O'Neil Clinical Research Center	Topeka	Kansas
United States	Southern Arizona VA Medical Center	Tucson	Arizona
United States	Tucson Medical Center	Tucson	Arizona
United States	Medstar Heart & Vascular Institute	Washington	District of Columbia
United States	Novant Health	Winston-Salem	North Carolina

Sponsors (5)

Lead Sponsor	Collaborator
On-X Life Technologies, Inc.	Acelis Connected Health, Avania, Clinipace Worldwide, WCG IRB

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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 — View 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 — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thromboembolism	Rate of thromboembolism evaluated every 100 patient-years	8 years
Primary	Valve Thrombosis	Rate of thrombosis evaluated every 100 patient-years	8 years
Primary	Bleeding Events	Rate of major and minor bleeding events evaluated every 100 patient-years	8 years
Secondary	Valve-Related Events	Rates of other valve-related events (e.g. prosthetic valve dysfunction, hemolysis, hemolytic anemia, endocarditis) every 100 patient-years	8 years
Secondary	New York Heart Association (NYHA) classification	Functional classification at each follow-up	8 years
Secondary	Valve Hemodynamics	Echocardiograpic measures of valve hemodynamics at 1, 3 and 5 years	5 years