Thermotherapy compared with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous Leishmaniasis in Ethiopia: A phase II randomized controlled trial

Cutaneous leishmaniasis (CL) is a significant public health challenge in Ethiopia with an estimated 20,000–30,000 new cases annually. Despite this high disease burden, management is constrained by limited therapeutic options and lack of local clinical trial evidence to guide routine care. This multicenter, randomized, controlled, open-label, adaptive Phase II/III trial in Ethiopia compared a single thermotherapy (TT) session (50 °C, 30 s) with weekly intralesional sodium stibogluconate (IL-SSG V ) for 4–6 weeks. Adults aged 18–60 years with parasitologically confirmed, uncomplicated localized cutaneous leishmaniasis were enrolled. Initial cure (evaluated at day 90/105) and final cure (day 180) were assessed using both per-protocol (PP) and intention-to-treat (ITT) analyses. Prespecified futility and interim analysis were conducted to guide phase progression. Based on recommendations from an independent Data and Safety Monitoring Board, the final phase II analysis included 183 participants. Of the 183 participants included for the final phase II analysis, 91 randomized to the TT arm and 92 to the IL-SSG V arm. Participants were predominantly male, 55 (60.4%) in the TT arm, while 49 (53.3%) in the IL-SSG V arm. The median age of participants was 27 years (IQR: 19–39). In ITT, initial cure rates were 44.0% ( n = 40) for TT and 52.2% ( n = 48) for IL-SSG V , demonstrating no statistically significant difference ( p = 0.266). Final cure rates were 34.1% ( n = 31) for TT and 43.5% ( n = 40) for IL-SSG V ( p = 0.191). In PP analysis, the final cure rate was 39.2% in the TT and 57.6% in the IL-SSG arm, showing a statistically significant difference ( p = 0.032). No serious adverse events were reported. The observed adverse events were mild and resolved without complications. Health-related quality of life improved significantly in both arms post-cure (z = 7.22, p = 0.001). While the per-protocol analysis revealed a lower final cure rate for TT than IL-SSG V , intention-to-treat efficacy was comparable. Notably, TT demonstrated better adherence and an acceptable safety profile. In resource-limited Ethiopian settings—where most CL cases remain untreated and risk lifelong disfigurement—TT provides a pragmatic, single-session alternative where IL-SSG V access is constrained. This trial was registered in the Pan African Clinical Trials Registry with trial number PACTR202205775486864 on 30 May 2022.