The CLTI Paradigm Shift: Implications for Clinical Trial Design and Endpoints in Endovascular Management of Infrapopliteal Disease

Abstract

The evolution from critical limb ischemia to chronic limb-threatening ischemia (CLTI) necessitates a reevaluation of clinical trial endpoints. Traditional measures like hemodynamic indices and lesion patency inadequately reflect CLTI complexity or patient-centered outcomes. This article explores the limitations of conventional endpoints and proposes a modified definition of clinically-driven target lesion (TL) revascularization (CD-TLR) that addresses inflow, TL, and outflow disease. By incorporating a more comprehensive assessment of vascular health and prioritizing patient-relevant outcomes, this modified CD-TLR definition may better reflect modern CLTI management strategies and improve clinical relevance of trial results in this challenging patient population.

Clinical Impact

The evolution from CLI to CLTI requires reassessing how we measure treatment success in clinical trials. This review identifies why traditional endpoints like hemodynamic indices, lesion patency, and CD-TLR may not adequately inform clinical decision-making. The importance of measuring outcomes that directly impact patient quality of life will help clinicians better evaluate and apply clinical trial results. An emphasis on limb salvage, wound healing, and functional outcomes, rather than surrogate endpoints alone, will lead to more informed treatment decisions and improved CLTI management strategies.