Complete ulcer healing as primary endpoint in studies on critical limb ischemia? A critical reappraisal

Objectives. Although complete ulcer healing is the mandatory primary efficacy criterion in current European guidelines for drug trials in critical limb ischemia (CLI), the appropriateness of this endpoint has been questioned for some time. We carried out a systematic review to assess the value of this endpoint in studies on reconstructive measures, considered to be the standard of care for CLI. Methods. A computerized literature search (1985-2005) was performed to track down clinical studies on endovascular and surgical interventions by using the search terms CLI and ulcer healing and their synonyms. Results. 1,914 papers on revascularization in CLI were identified. Complete ulcer healing was reported in 17 studies (0.9%). Among these, there were no randomized controlled trials, five prospective cohorts on endovascular procedures, and six retrospective cohorts for endovascular and surgical procedures, respectively. If healing rates or time to ulcer healing were available, they differed greatly between the studies without consistent correlation to types of therapy. Conclusions. In past and current literature, complete ulcer healing is not a consistently reported criterion for success of revascularization in CLI. Thus, its appropriateness for efficacy assessment of drug studies in CLI patients has to be questioned.