Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia

Abstract

For new catheter-based therapies in CLI, OPGs offer a feasible approach for pre-market evaluation using non-randomized trial designs. Such studies should incorporate risk stratification in design and reporting as the CLI population is heterogeneous with respect to baseline variables and expected outcomes. Guidelines for CLI trial design to address consistency in study cohorts, methods of assessment, and endpoint definitions are provided.

Critical Limb Ischemia: Current Trends and Future Directions

“…BASIL‐2 (ISRTCN.com: ISRTCN27728689), Bypass versus Angioplasty in Severe Ischemia of the Leg‐2, funded by the National Health Service (NHS), investigates venous bypass first versus best endovascular first strategy in 600 patients with severe limb ischemia due to infrapopliteal atherosclerotic disease in a 1:1 randomized fashion, while BASIL‐3 (not yet initiated) will be a 3‐armed trial that will compare plain balloon angioplasty, drug‐eluting balloon, and drug‐eluting stents in severe limb ischemia patients due to femoropopliteal lesions. These trials will also include several of the recently defined Objective Performance Goals as outcome measures 11. These large and ambitious trials will provide very essential information on characteristics and prognosis of severe limb ischemia and more current evidence to guide therapy for this challenging pathology.…”

Outcomes for Clinical Studies Assessing Drug and Revascularization Therapies for Claudication and Critical Limb Ischemia in Peripheral Artery Disease

“…Although some groups support singlearm studies against optimal performance criteria, particularly for PAD device-based therapies, 62,63 they may provide an air of legitimacy that could bias providers and impede the completion of randomized trials assessing their efficacy compared with standard treatment.…”

“…7 However, doubts about the objectivity of measuring pain at rest and partial ulcer healing limit the validity of these end points. 62 Because cardiovascular end points are particularly high in patients with critical limb ischemia, they are often considered in composite primary or secondary end points for critical limb ischemia. 7 Over the last decade, percutaneous revascularization has increasingly been a major treatment option for symptomatic PAD, but the principles of these guidelines are not always used in clinical trials.…”

“…62 In an extension of the coronary literature, 9 target lesion revascularization (any repeat percutaneous revascularization to the target lesion or bypass surgery to the target vessel) and target vessel revascularization (any revascularization to any segment of the target vessel) are common end points in percutaneous peripheral revascularization trials. 49,50 A key issue with repeat revascularization is whether it is influenced by symptoms or by imaging (duplex ultrasound or angiography).…”

Hospital Readmissions Following Endovascular Therapy for Critical Limb Ischemia: Associations With Wound Healing, Major Adverse Limb Events, and Mortality

“…In addition, whereas major amputation or major adverse limb events (MALE) are frequently used as outcomes in studies of patients with CLI,5 these endpoints do not capture readmission or the presence of persistent ulcers, both of which may significantly impact quality of life.…”