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

@article{agbanyo2026highdose,
  title = {{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}},
  author = {Abigail Agbanyo and Yaw Ampem Amoako and Charles Opondo and Michael Ntiamoah Oppong and Adwoa Asante-Poku and Jacob Novignon and Joseph Tuffour and Ishaque Saim Mintah and Ruth Dede Tuwor and Dzifa Kofi Ahiatrogah and Richard Adjei Akuffo and Miriam Gborglah and Iris Mosweu and Catherine Pitt and Elizabeth Allen and Stephen L. Walker and Dorothy Yeboah-Manu and Michael Marks and Richard Odame Phillips and SHARP Collaboration},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014783},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014783},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - 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
AU  - Abigail Agbanyo
AU  - Yaw Ampem Amoako
AU  - Charles Opondo
AU  - Michael Ntiamoah Oppong
AU  - Adwoa Asante-Poku
AU  - Jacob Novignon
AU  - Joseph Tuffour
AU  - Ishaque Saim Mintah
AU  - Ruth Dede Tuwor
AU  - Dzifa Kofi Ahiatrogah
AU  - Richard Adjei Akuffo
AU  - Miriam Gborglah
AU  - Iris Mosweu
AU  - Catherine Pitt
AU  - Elizabeth Allen
AU  - Stephen L. Walker
AU  - Dorothy Yeboah-Manu
AU  - Michael Marks
AU  - Richard Odame Phillips
AU  - SHARP Collaboration
PY  - 2026
DA  - 2026/09/29
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014783
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014783
AB  - 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). Author summary: Buruli ulcer (BU) is a neglected tropical disease that causes destructive skin lesions and long-term disability, particularly in rural communities. The current standard treatment, eight weeks of rifampicin and clarithromycin, is effective but lengthy, which can reduce adherence and increase the burden on patients and health services. This study explored whether a high-dose rifampicin regimen could offer a safe, shorter, and more convenient alternative. In a randomized clinical trial conducted in Ghana, we compared a 4-week high-dose rifampicin regimen with the standard 8-week treatment. We assessed how quickly the bacteria causing BU were cleared from the wounds of affected individuals and monitored safety outcomes. The results showed that the shorter, high-dose regimen was not superior but was well tolerated and achieved similar bacterial clearance and healing times compared to standard treatment although we enrolled fewer participants than planned and the intervention and control groups were not evenly balanced. Notably, patients receiving the high-dose regimen experienced fewer paradoxical reactions, a common inflammatory complication during treatment. These findings suggest that high-dose rifampicin may offer a promising strategy to shorten BU treatment time. However, larger studies are needed to confirm its efficacy, safety and potential to shorten treatment duration while maintaining good outcomes.
SN  - 1935-2735
ER  -