In September 2014, the BEST-CLI (Best endovascular vs. best surgical therapy in patients with critical limb ischemia) trial started enrolling patients in North America. This study aims to compare the efficacy, functional outcomes and cost of endovascular therapy versus open surgical bypass in patients with critical limb ischaemia and infrainguinal peripheral arterial disease. BEST-CLI is a prospective, randomised, multicentre trial that aims to enrol 2,100 subjects at 120 sites across the United States and Canada. The US$25 million in funding, granted by the National Heart, Lung, and Blood Institute (NHLBI), will also be used to measure comparative quality of life and cost-effectiveness through a robust Cost Effectiveness Core. The Clinical Coordinating Center is based at the Brigham and Women’s Hospital and includes the three authors of this article. The Data Coordinating Center is at the New England Research Institutes (NERI, Watertown, USA).
The BEST-CLI trial has a two cohort design: Cohort 1 includes patients with adequate single segment great saphenous vein and Cohort 2 includes those without adequate single segment great saphenous vein. The former will allow comparison of endovascular therapy with infrainguinal bypass using the best possible conduit. Patients are stratified based on clinical presentation and arterial anatomy and are randomised 1:1 into the open surgical bypass or endovascular therapy arms. Once a patient is randomised, the definition of “best treatment” is left up to the investigator, with most commercially available standard of care endovascular therapies allowed, as well as all surgical bypass techniques and conduits. All patients enrolled will be followed for at least two years post-procedure. As the trial progresses, new therapies will be considered for inclusion as deemed appropriate. As a timely example of this process, both the Bard Lutonix 035 and the Medtronic Admiral drug-coated balloons, recently approved by the FDA, were reviewed and recently approved for use in the trial. This strategy, along with the overall pragmatic design of the BEST trial, are aimed at ensuring the study remains current and relevant.
This study will utilise a novel primary endpoint, major adverse limb event-free survival, defined as survival without above-the-ankle amputation of the index limb or major reintervention. It promises to be more relevant in the comparison of limb-related outcomes than the commonly used amputation-free survival endpoint. BEST-CLI also includes other relevant endpoints seldom seen in critical limb ischaemia trials, including reintervention and amputation-free survival, freedom from haemodynamic failure, freedom from clinical failure and freedom from critical limb ischaemia.
The BEST-CLI trial aims to include all specialists who treat critical limb ischaemia at each participating institution. To that end, at every trial site, “critical limb ischaemia teams”, designed to foster interdisciplinary cooperation, have been created that include interventional cardiologists, vascular surgeons, interventional radiologists, vascular medicine specialists, research nurses and research coordinators.
This multidisciplinary approach is no more evident than within the well-balanced Executive Committee. Members include representatives from interventional cardiology, Chris White (co-chair); interventional radiology, John Kaufman and Michael Dake; vascular medicine, Mark Creager and Michael Jaff; and vascular surgery, Michael Conte (co-chair) and Richard Powell. The Executive Committee also includes principal investigators of the CCC (Farber, Menard and Rosenfield), the Data Coordinating Center (Sandi Siami and Susan Assmann), the Cost Effectiveness Analysis Core (Niteesh Choudry and Jerry Avorn) and the NHLBI Project Officials, Diane Reid and George Sopko. The BEST-CLI Executive Committee has to date and will continue to provide invaluable oversight leadership to the trial.
BEST-CLI has received formal endorsements of support from many professional associations, including the Society for Vascular Surgery, Society of Interventional Radiology, Society for Vascular Medicine, Vascular Disease Foundation, Society for Cardiac Angiography and Interventions, Vascular Interventional Advances and the Food and Drug Administration.
There is tremendous variability across the world as to how patients with critical limb ischaemia are managed. The significant equipoise reflected in the widely disparate practice patterns seen throughout North America and other parts of the world serves to underscore the need for a trial of this scope and nature. BEST-CLI’s findings will help both clinicians treating critical limb ischaemia and patients suffering from it.
For more information on the BEST-CLI trial, please visit www.BESTCLI.com. If you are interested in becoming a clinical site, please email [email protected] or contact Alik Farber ([email protected]), Matthew Menard ([email protected]) or Ken Rosenfield ([email protected]).
Alik Farber is chief of Vascular and Endovascular Surgery at Boston Medical Center, Boston, USA; Matthew Menard is co-director of Endovascular Surgery at the Brigham and Women’s Hospital, Boston, USA; and Kenneth Rosenfield is section head of Vascular Medicine and Intervention in the Division of Cardiology at the Massachusetts General Hospital, Boston, USA