Learn more about the PROACT Study
Prospective Randomized On-X® Valve Reduced Anticoagulation Clinical Trial (PROACT)
The U.S. Food and Drug Administration (FDA) has approved an investigational device exemption (IDE) clinical trial of the On-X® Prosthetic Heart Valve at reduced anticoagulation levels following review and approval by clinical centers. Successful completion of the clinical study could result in the On-X® valve becoming the only mechanical heart valve approved for low-dose anticoagulation therapy.
Based on existing clinical data and the submitted protocol, the FDA has determined that a clinical trial of the On-X® valve with three specific patient groups at reduced anticoagulation levels is clinically reasonable. The patient groups include low-risk aortic valve replacement patients, higher risk aortic valve replacement patients and mitral valve replacement patients. Higher risk patients include those with heart rhythm problems, left ventricular dysfunction, previous thrombo-embolism and condition of hypercoagulability.
The low-risk aortic patient group will be maintained using non-warfarin anticoagulation medication of clopidogrel (Plavix®) and aspirin. Higher-risk aortic patients will be maintained using warfarin (Coumadin®) at reduced International Normalized Ratio (INR) levels of between 1.5 and 2.0, plus aspirin. The mitral valve replacement patients will be maintained with warfarin at a target INR of 2.0 to 2.5 and aspirin. The first three months for all patient groups include traditional warfarin anticoagulation protocols. To ensure that patients remain within target INR range, each patient will be required to self-monitor their anticoagulation levels. Results of this self-monitoring will be communicated to the patient's physician.
The investigation will be led by John D. Puskas, M.D., associate chief, Division of Cardiothoracic Surgery at Emory University School of Medicine in Atlanta, Ga., and is expected to be complete after five years of follow-up. It will involve 40 centers and 1200 patients.
"This is the first FDA trial to explore lower anticoagulation with mechanical heart valves," said Dr. Puskas. The On-X® valve has design and material features that make us hopeful that it may function well at lower levels of blood-thinning medications. If this trial proves what we believe it will, On-X® valve recipients will be able to take a lower level of anticoagulant, which will reduce the potential incidence of bleeding complications caused by taking the higher dosages of Coumadin normally prescribed after receiving a mechanical heart valve."
According to The American College of Cardiology and the American Heart Association's Guidelines for Management of Patients with Valvular Heart Disease," the standard of care for three-months postoperatively is anticoagulation therapy with warfarin at an INR of 2.5 to 3.5 for both mechanical and biological (animal) tissue valve replacement patients. Recommendations for biological valve patients three months postoperatively are 80 to 100 mg/day of aspirin. After three months, mechanical valve postoperative anticoagulation therapy advises the use of warfarin at INR levels of 2.0 to 3.0 for aortic valve replacement patients without risk and 2.5 to 3.5 for aortic valve patients with risk and mitral valve patients. Although warfarin has a long history of safe use, it has the potential side effect of bleeding.
"The 'holy grail' for cardiac surgeons implanting heart valves has been 'A Valve for Life'," said Sidney Levitsky, M.D., Cheever Professor of Surgery at Harvard Medical School and director of Cardiothoracic Surgery for CARE Group, Boston, Mass., and chair of the Reduced Anticoagulation Clinical Trial of the On-X® Prosthetic Heart Valve Data Safety Monitoring Committee. "To avoid clotting, presently accepted mechanical valve postoperative care mandates high levels of anticoagulation with warfarin, which is associated with bleeding problems varying from minor episodes of hematuria (blood in urine) and melena (blood in stool) to intracerebral hemorrhage. If the approved FDA reduced anticoagulation study is successful, the On-X® valve will become the safe valve of choice for a new generation of patients who are expected to enjoy a long life, and we will finally approach the concept of 'A Valve for Life'."
"The On-X® valve may be the next step in the evolution of valve technology," said Hillel Laks, M.D., professor and chief of Cardiothoracic Surgery and director of the Heart, Lung and Heart-Lung Transplant Programs at UCLA School of Medicine. "This study is significant because of the larger numbers of older valve patients who are living longer. Traditionally, these patients would receive tissue valves to avoid the bleeding risk associated with taking higher levels of Coumadin. However, when tissue valve patients live into their 80s and 90s, they run the risk of having replacement surgery in eight to 16 years when the tissue valve wears out. This FDA study has the potential for changing our choices in heart valves in the future. If we can show that it is safe to use a mechanical valve with low levels of Coumadin or alternative drugs that are safe - or even no Coumadin - the choice in these borderline older patients will be completely different."
"After decades of heart valve research and design, we have developed what could be the first prosthetic heart valve to combine the durability of a mechanical valve with the reduced complication rates of tissue valves," said Jack Bokros, Ph.D.,On-X LTI's founder and chairman. "The approval to conduct this reduced anticoagulation study is further evidence that the On-X® valve merits study under this protocol. The success of the study could provide proof that the On-X® valve is truly a breakthrough medical advance in heart valve prosthetics, providing patients with the benefits of both mechanical and tissue valves: a valve that will last a lifetime without the potential complications of taking high dose anticoagulants."
Clinical centers and patients are now being recruited for the On-X® reduced anticoagulation study. The study is limited to 1,200 patients and 40 institutions. Interested parties should contact John Ely, Executive Vice President of Regulatory and Clinical Affairs forOn-X LTI, at 888-339-8000 ext. 226 or ely@mcritx.com. Information and updates for this and other On-X® Prosthetic Heart Valve studies are located at www.onxlti.com or by contacting On-X LTI.
