Understanding objective performance goals for critical limb ischemia trials.

Area of Science:

• Vascular Surgery
• Clinical Trial Design
• Peripheral Arterial Disease Research

Background:

• Critical limb ischemia (CLI) is the advanced stage of peripheral arterial disease, leading to high limb loss and mortality rates.
• Surgical bypass is the standard for limb salvage, but less-invasive endovascular therapies lack robust efficacy data for CLI.
• Clinical trials for CLI are complex due to undefined cohorts and endpoints, hindering device development.

Purpose of the Study:

• To establish objective performance goals (OPGs) for critical limb ischemia (CLI) to serve as therapeutic benchmarks.
• To facilitate the premarket assessment of new revascularization devices for CLI.
• To define key endpoints and high-risk subgroups for future CLI clinical trials.

Main Methods:

• Analyzed data from three large randomized controlled trials of surgical bypass for CLI.
• Defined a major adverse limb event (MALE) as a composite endpoint including amputation or major vascular reintervention.
• Developed risk-adjusted OPGs for specific high-risk CLI subgroups based on clinical, anatomical, and conduit characteristics.

Main Results:

• Established nine safety and efficacy measures for CLI device assessment, using surgical bypass as the comparator.
• Suggested freedom from perioperative death or MALE (MALE + POD) as a primary efficacy endpoint, with a 76.9% success rate in surgical bypass controls at 1 year.
• Defined high-risk subgroups (e.g., age >80, tissue loss, infrapopliteal disease, poor vein quality) with corresponding risk-adjusted OPGs.

Conclusions:

• The developed OPGs provide new benchmarks for evaluating revascularization therapies in CLI.
• These benchmarks are expected to streamline clinical trial design and accelerate the development of novel devices for CLI.
• Standardized endpoints and performance goals are crucial for advancing limb salvage in critical limb ischemia.