Shortening Buruli ulcer treatment in western Africa: an update on the BLMs4BU trial

Abstract

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d135795e372">Introduction: For Buruli Ulcer (BU), the World Health Organization (WHO) recommended the administration of rifampicin (R) and clarithromycin (C) for 8 weeks (RC8). Preclinical studies have demonstrated that the combination of amoxicillin/clavulanate (A) and RC is highly effective in vitro against Mycobacterium ulcerans. The aim is to evaluate the non-inferiority of a 4-week regimen of A combined with RC (RCA4) versus standard WHO recommended treatment (RC8) in achieving cure rates at month 12 post-treatment initiation <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d135795e374">Methods: The trial comprises randomized, open-label, non-inferiority, multicenter phase II and III studies. Patients were actively and passively recruited and included after clinical diagnosis (Very Likely or Likely WHO BU score), confirmed by qPCR IS2404, stratified according to BU lesion category and followed up for 12 months with standardized management. Primary efficacy outcome is the proportion of patients with complete healing of lesions without recurrence and without major surgical excision within 12 months of initiating treatment. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d135795e376">Results: The Phase II trial in Benin recruited 152 participants. Female-male distribution was balanced, with around 51% of participants aged &lt; 15 years. Over 96% of participants had a single lesion. Category III lesions were more frequent (44 %). Treatment allocation is balanced between the two arms. 98 completed follow-ups at 12 months, and none required major excision surgery. Only mild and transient adverse events or side effects were recorded. Since the recruitment is completed (80% power requirement), the RCA4 demonstrates its safety. A non-inferiority assessment of efficacy will be carried out at the end of the study. The Phase III trial is currently underway and has recruited 72 participants in Togo and Côte d'Ivoire. <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d135795e378">Conclusion: This shorter, all-oral, widely adapted treatment could establish a new paradigm in BU.