Determinants of enrolment rate in 397 clinical trials for healing diabetic foot ulcers: a systematic review.

OBJECTIVES

Diabetes mellitus (DM) affects over 422 million individuals globally. Diabetic foot ulcers (DFUs) stand out as a challenging complication of DM, affecting up to 34% of individuals with DM. Despite the prevalence of DFUs, clinical trials for DFUs often face slow and insufficient patient recruitment. We aimed to identify key determinants that impact subject recruitment rates in DFU clinical trials.

DESIGN

Systematic review.

DATA SOURCES

ClinicalTrials.gov and PubMed were searched to identify DFU clinical studies published from 1 January 1990 to 9 April 2025.

ELIGIBILITY CRITERIA

We included English-language publications of clinical trials aimed at healing DFUs that reported enrolment numbers, duration of enrolment and number of study centres.

DATA EXTRACTION AND SYNTHESIS

Records were extracted and subjected to two independent rounds of review by five authors (LZ, SP, RN, HL-T, and RK). Data were pooled and analysed using negative binomial regression, Kaplan-Meier methods and Cox proportional hazards models. Study enrolment and site enrolment rates, as well as time to complete study enrolment, were analysed. Between-study heterogeneity was assessed using the likelihood ratio test.

RESULTS

397 trials involving 31 955 participants were included. On average, DFU studies enrolled 4.24 patients per month (median: 1.65). US-based studies had slower recruitment than non-US studies, with a mean enrolment rate of 1.51 patients per site per month (median: 0.58). The average time to complete enrolment was 1.28 years. Studies that employed a higher number of study sites, were conducted outside the USA, studied behavioural or dietary supplement interventions, and began enrolment more recently, were more likely to have a higher enrolment rate. Longer time to complete enrolment was associated with a larger number of study sites, trials involving at least one US site, earlier starting enrolment year, and longer follow-up duration.

CONCLUSIONS

These findings have potential practical implications for the design and conduct of future DFU trials.