Objective Outcome Measures for Trials in Patients With Chronic Limb-Threatening Ischemia Across 2 Decades: Analysis and Recommendations

Vladimir Lakhter, Mitchell D. Weinberg, Andrew Galmer, Suraj Mishra, Raj Dalsania, Shinjita Das, Patrick J. Geraghty, Michael R. Jaff, Peter A. Schneider, Ido Weinberg

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Chronic limb-threatening ischemia (CLTI) is prevalent and associated with morbidity and mortality. The published research concerning CLTI therapeutics is evolving. The goals of this review are to: 1) summarize the endpoints that are being used in trials assessing interventions for patients with CLTI; and 2) review gaps and discrepancies in current outcome definitions. A search was conducted of the PubMed database and ClinicalTrials.gov to identify studies published between January 2000 and March 2020 that evaluated treatment options for patients with CLTI. Meta-analyses, case series, case reports, abstracts, and expert opinion were excluded. Forty-nine studies (n = 11,667) were identified that fulfilled the inclusion criteria. Most trials reported clinical outcomes (mortality, 69.4%; limb events, 87.8%; target lesion revascularization, 83.7%). Mean follow-up duration was 23.7 months. In investigational device exemption trials, total follow-up and follow-up to primary outcomes were discordant (12 months vs 6 months; P = 0.0018). Hemodynamic testing was reported in 71.4%, usually ankle-brachial index. Patency was assessed in 89.8% of trials; ultrasound was used in 65.3% and invasive angiography in 85.7%, at baseline and/or during follow-up. Wound assessment was performed in 49.0% of studies, qualitative in 28.6% and quantitative in 20.4%. Finally, quality of life assessment was performed in 55% of studies. Definitions for many outcomes varied across studies. Consensus regarding which outcomes to study, uniform definitions, and optimal methods to measure some of these outcomes are yet to be established. A comprehensive effort by all stakeholders is needed to move the field of CLTI forward.

Original languageEnglish
Pages (from-to)2584-2597
Number of pages14
JournalJACC: Cardiovascular Interventions
Issue number23
StatePublished - Dec 13 2021


  • CLI
  • CLTI
  • chronic limb-threatening ischemia
  • clinical trial
  • critical limb ischemia


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