High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana

Journal article

BACKGROUND: The current 8-week regimen of rifampicin and clarithromycin for Buruli ulcer (BU) is suboptimal. High-dose rifampicin could shorten treatment and improve outcomes. We evaluated whether a 4-week high-dose regimen could improve time to clearance of viable Mycobacterium ulcerans. METHODOLOGY: In this open-label, individually randomised trial conducted in Ghana, participants with PCR-confirmed BU were assigned (1:1) to either high-dose oral rifampicin (20mg/kg) with clarithromycin (15mg/kg) for 4 weeks (HR) or standard-dose rifampicin (10mg/kg) with clarithromycin (15mg/kg) for 8 weeks (SR). All wounds were dressed with DACC-coated dressings. The primary outcome was time to clearance of viable M. ulcerans assessed by 16S rRNA qPCR up to week 20. FINDINGS: Between 26th November 2021 and 31st July 2024, 42 participants were randomised (HR:23, SR:19), which was short of the target (n = 112). The mean time to clearance was 4.9 weeks (SE 1.4) in the HR arm versus 7.0 weeks (SE 1.9) in the SR arm, with an adjusted mean difference of -0.5 weeks (95%CI -5.0 to 4.1, p = 0.835). No recurrences occurred in either arm. Paradoxical reactions were observed in 0/21 participants in the HR arm vs. 5/15 in the SR arm (adjusted OR 0.19, 95%CI 0.00-1.35, p = 0.102). Secondary infection rates were similar between groups. CONCLUSION: High‑dose rifampicin combination for 4 weeks was well tolerated in this population. A nominally lower proportion of paradoxical reactions was observed in the high-dose rifampicin arm compared with standard therapy. The trial did not find evidence of significantly shorter time to microbiological clearance or healing compared with standard therapy. Larger trials are needed to determine efficacy and safety. TRIAL REGISTRATION: Pan African Clinical Trials Repository, trial registration number: PACTR202011867644311 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=14534).

Authors: Agbanyo, A; Amoako, YA; Opondo, C; Oppong, MN; Asante-Poku, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS Neglected Tropical Diseases
• Volume: 20
• Issue: 9
• Pages: e0014783-e0014783
• Publication date: 2026-09-29
• Acceptance date: 2026-09-04
• DOI: 10.1371/journal.pntd.0014783
• EISSN: 1935-2735
• ISSN: 1935-2727
• Language: English
• Keywords: microbiological clearance; paradoxical reaction; West Africa; drug safety and tolerability; secondary infection; Ghana; clarithromycin; wound healing; rifampicin; treatment time reduction; Mycobacterium ulcerans; high-dose rifampicin; Buruli ulcer; short-course antibiotic therapy