Contemporary Chronic Limb-Threatening Ischemia Care in the United States - Part 2 - Designing Clinical Device Trials

Sep 29, 2026

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Head-to-head research comparing invasive revascularization strategies for chronic limb-threatening ischemia (CLTI) remains limited due to major obstacles in randomized controlled trial execution. Challenges include trial expense, refining patient selection for real-world applicability, and defining optimal study end points. The Vascular InterVentional Advances (VIVA) Foundation convened a multispecialty forum to discuss and improve medical device trial design, summarizing current clinical evidence and proposed comparative-trial options across specialties. Four key optimization domains were identified.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Clinical trial design challenges in CLTI

VIVA forum and collaborative trial design approach

Optimization domains for comparative trials

Journal of the Society for Cardiovascular Angiography & Interventions 4 (2025) 103934 Proceedings Contemporary Chronic Limb-Threatening Ischemia Care in the United States—Part 2: Designing Clinical Device Trials Eric A. Raghu Secemsky, MD, MSc a, *, Ehrin J. Armstrong, MD b, Venita Chandra, MD c, Kolluri, MD, MS d, Saher S. Sabri, MD e, Niten Singh, MD f a Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; b Department of Interventional Cardiology, Advanced Heart and Vein Center, Denver, Colorado; c Division of Vascular Surgery, Stanford University Medical Center, Stanford, California; d Cardiovascular Service Line – OhioHealth Riverside Methodist Hospital, Columbus, Ohio; e Division of Interventional Radiology, MedStar Georgetown University Hospital, Washington, DC; f Division of Vascular Surgery, Department of Surgery, Harborview Medical Center, Seattle, Washington | A B S T R A C T | | --- | | Head-to-head research comparing invasive revascularization strategies for chronic limb-threatening ischemia (CLTI) is sparse, partly due to challenges in conducting randomized controlled trials in the CLTI space. These include the expense of head-to-head trials, optimizing patient selection criteria for real-world applicability, and identifying optimal study end points. The Vascular InterVentional Advances (VIVA) Foundation, a 501(c)(3) not-for-profit organization, convened a Vascular Leaders Forum to initiate an open, multispecialty collaborative discussion of these challenges and ways to optimize the design of medical device trials in CLTI. This article summarizes the current landscape of clinical studies of CLTI revascularization strategies and options for designing comparative trials proposed by representatives from vascular surgery, interventional cardiology, interventional radiology, vascular medicine, podiatry, the U.S. Food and Drug Administration, and a medical device manufacturer. Four broad areas to optimize comparative trials of CLTI interventions were identified. First, primary end points should be carefully chosen with attention to clinical, patient-centric, imaging, and hierarchical considerations; standardization; and inclusion of guideline-directed medical therapy. Second, broader eligibility criteria can expand and hasten enrollment and are important for gathering evidence on outcomes in medically complex patients often encountered in real-world practice. Third, extending the primary end point timing to 12 months with additional follow-up out to 24 to 60 months would accommodate a longer period of device evaluation and the ability to enrich clinical end-point rates. Finally, innovative pragmatic trial designs and statistical methodologies are needed to conduct comprehensive, cost effective, relevant trials with sufficient statistical power and without prohibitively large sample sizes and study durations. | Introduction Chronic limb-threatening ischemia (CLTI) affects approximately 11% of patients with peripheral artery disease (PAD) and represents the most severe end of the PAD spectrum.1 , 2 CLTI is defined as PAD in combination with rest pain, lower limb ulceration, or gangrene of more than 2 weeks duration.1 It is associated with significant mortality, limb loss, pain, health care costs, and diminished quality of life (QOL) .1–5 With the worldwide prevalence of PAD increasing over the last 3 decades,6–8 determining the most efficacious revascularization approaches for CLTI is imperative. The combination of endovascular or surgical revascularization along with best medical therapy, wound care, smoking cessation, diet, and exercise aims to improve limb salvage and survival and maximize QOL.1 , 9 However, there is a dearth of head-to-head research comparing CLTI revascularization strategies and combinations of approaches. Barriers to conducting randomized controlled trials (RCTs) in the CLTI space are substantial. These include the expense of head-to-head trials, un

FAQs

Why is head-to-head research for CLTI revascularization strategies limited?

Head-to-head comparisons are sparse because randomized controlled trials in the CLTI setting face substantial challenges, including high costs, difficulties optimizing patient selection for real-world use, and identifying appropriate study end points.

What was the purpose of the VIVA Foundation’s Vascular Leaders Forum?

The forum was convened to initiate an open, multispecialty discussion on CLTI trial design challenges and practical ways to optimize medical device trials, bringing together representatives from multiple specialties, FDA, and a device manufacturer.

What four broad areas were identified to optimize comparative CLTI device trials?

The article identifies four main optimization areas: careful selection of primary end points, broader eligibility criteria to speed enrollment, extending primary end-point timing with longer follow-up, and using innovative pragmatic trial designs and statistical methods to improve relevance and power.

Sep 29, 2026

Upload by Stanley