Researchers awarded $25 million NIH grant to study critical limb ischemia treatment

Trial will provide guidance on cost-effective ways to treat this severe form of peripheral artery disease

A team of researchers from Brigham and Women's Hospital (BWH), Boston Medical Center (BMC) and Massachusetts General Hospital (MGH) has been awarded $25 million by the National Institutes of Health (NIH) to conduct a four-year, randomized clinical trial-the BEST-CLI Trial (Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia). The trial will compare traditional bypass surgery with the less invasive alternative of endovascular treatment for patients with critical limb ischemia (CLI).

The principal investigators of the BEST-CLI trial are Alik Farber, MD, division chief of Vascular and Endovascular Surgery at BMC; Matthew Menard, MD, co-director of Endovascular Surgery at BWH; and Kenneth Rosenfield, MD, section head of Vascular Medicine and Intervention at MGH.

CLI is the most severe form of peripheral arterial disease, which is caused by chronic inflammation and atherosclerotic plaque build-up in the arteries of the legs. Symptoms caused by reduced blood flow to the legs and feet include ischemic leg pain, non-healing wounds and gangrene. If untreated, CLI can often lead to leg amputation. The aging of the national population and the rising rate of diabetes have led to an increase in both peripheral arterial disease and CLI.

According to the study investigators, while both open surgery and endovascular interventions are used to treat CLI, it is not clear which approach works best in patients who are candidates for both treatment options.

"Currently, there is a lack of consistency and clarity as to what approach-minimally invasive endovascular or open surgery-is best for our patients," said Farber. "The BEST-CLI Trial will provide answers to many unanswered questions, most importantly what treatment works best for whom."

"The CLI population is an exceptionally complex and challenging group of patients to treat," added Menard. "In addition to providing much needed information on the functional outcomes and cost-effectiveness of the two treatment strategies being tested, the BEST-CLI Trial will provide a unique opportunity for interdisciplinary collaboration between all of the subspecialties currently providing care to CLI patients.

Added Rosenfield: "The BEST-CLI Trial will be a robust and rigorously conducted clinical trial which promises to greatly enhance our understanding of CLI-a devastating disorder that affects millions of Americans. We are grateful to the National Institutes of Health for recognizing the enormous impact of this scourge and look forward to expanding the evidence base to optimize care and outcomes for these patients with advanced cardiovascular disease."

The BEST-CLI trial will be highly innovative in both its design and its collaborative nature. It will provide, for the first time, urgently needed clinical guidance for CLI management by using:

• a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available;
• a novel primary endpoint that includes limb amputation rates, repeat treatments and loss of life;
• a multi-disciplinary structure that fosters cooperation among vascular surgeons, interventional cardiologists, interventional radiologists and vascular medicine specialists; and
• novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the two treatment strategies being tested.

The trial will enroll 2,100 participants and be conducted at 120 clinical centers in the United States and Canada. The New England Research Institutes (Watertown, MA) will be serving as the data coordinating center.

Source: Brigham and Women's Hospital