Randomized On-X Anticoagulation Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT)

Conditions
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Heart Valve Disease

Intervention / Treatment
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* Device: On-X valve using reduced anticoagulation
* Device: On-X Valve with Standard warfarin Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVR Low Risk without warfarin<br>AVR Low Risk without warfarin | Device: On-X valve using reduced anticoagulation<br>* Valve replacement with antiplatelet agents or lowered warfarin<br>* Other names: On-X Prosthetic Heart Valve;|
| Active Comparator: AVR low risk with standard warfarin<br>AVR low risk with standard warfarin | Device: On-X Valve with Standard warfarin Therapy<br>* Valve replacement with standard dosage warfarin<br>* Other names: On-X Prosthetic Heart Valve;|
| Experimental: AVR High risk with lower warfarin<br>AVR High risk with lower warfarin | Device: On-X valve using reduced anticoagulation<br>* Valve replacement with antiplatelet agents or lowered warfarin<br>* Other names: On-X Prosthetic Heart Valve;|
| Active Comparator: AVR High Risk with standard warfarin<br>AVR High Risk with standard warfarin | Device: On-X Valve with Standard warfarin Therapy<br>* Valve replacement with standard dosage warfarin<br>* Other names: On-X Prosthetic Heart Valve;|
| Experimental: MVR with lower warfarin<br>MVR with lower warfarin | Device: On-X valve using reduced anticoagulation<br>* Valve replacement with antiplatelet agents or lowered warfarin<br>* Other names: On-X Prosthetic Heart Valve;|
| Active Comparator: MVR with standard warfarin<br>MVR with standard warfarin | Device: On-X Valve with Standard warfarin Therapy<br>* Valve replacement with standard dosage warfarin<br>* Other names: On-X Prosthetic Heart Valve;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolism | Rate of thromboembolism evaluated every 100 patient-years | 8 years | 
| Valve Thrombosis | Rate of thrombosis evaluated every 100 patient-years | 8 years | 
| Bleeding Events | Rate of major and minor bleeding events evaluated every 100 patient-years | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Valve-Related Events | Rates of other valve-related events (e.g. prosthetic valve dysfunction, hemolysis, hemolytic anemia, endocarditis) every 100 patient-years | 8 years | 
| New York Heart Association (NYHA) classification | Functional classification at each follow-up | 8 years | 
| Valve Hemodynamics | Echocardiograpic measures of valve hemodynamics at 1, 3 and 5 years | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prosthesis, valve, antithrombotics, randomized