The Prospective Randomized On-X Valve Anticoagulation Clinical Trial (PROACT)
Update: In April 2015 FDA approved the On-X aortic heart valve with INR 1.5–2.0 following 3 months of standard anticoagulation therapy based on the successful completion of the AVR high risk arm of the PROACT study.
In January of 2006, The US FDA approved the first and only IDE (Investigational Device Exemption) lowered anticoagulation trial for a mechanical heart valve to be conducted at 40 sites in the United States and Canada for the On-X Prosthetic Heart Valve. Successful completion of the clinical trial could result in the On-X heart valve becoming the only mechanical valve approved for low-dose anticoagulation therapy.
PROACT Test Groups
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 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.
On-X aortic valve with low-dose warfarin for higher risk patients – Study complete
This arm of the study compared the outcomes for On-X aortic valve patients with INR 1.5–2.0 (low-dose warfarin) and INR 2.0–3.0 (standard therapy). The low-dose warfarin group had 65% fewer bleeding events without a difference in thromboembolic events. This study included higher risk patients with heart rhythm problems, left ventricular dysfunction, previous thromboembolism and condition of hypercoagulability.
The successful completion of this arm of the study has resulted in FDA approval for On-X aortic heart valves with INR 1.5–2.0.
On-X aortic valve without warfarin for lower risk patients
In this arm of the study, On-X aortic valve patients are maintained using non-warfarin anticoagulation medication. The protocol for this arm of the study is currently under revision.
On-X mitral valve with low-dose warfarin
This arm of the study compares the outcomes for On-X mitral valve patients with INR 2.0–2.5 (low-dose warfarin) and INR 2.5–3.5 (standard therapy). Until the completion and analysis of study data, On-X LTI continues to recommend standard anticoagulation therapy for On-X mitral valve recipients.
More about PROACT
The investigation is led by John D. Puskas, M.D., Chairman of Cardiothoracic Surgery at Mount Sinai Beth Israel, and Director of Surgical Coronary Revascularization for the Mount Sinai Health System.
“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.”
CAUTION: Federal law restricts this device to sale by or on the order of a physician. Refer to the Instructions for Use that accompany each valve for indications, contraindications, warning, precautions and possible complications.
CAUTION: Investigational use of this device in the Prospective Randomized On-X Valve Anticoagulation Trial (PROACT) is limited by federal law to investigational sites.