03100nas a2200433   4500000000100000008004100001260001200042653001500054653001900069653001700088653003200105653001000137100001400147700001300161700001300174700001300187700001800200700001500218700001400233700001300247700001200260700001700272700001300289700001500302700001300317700001100330700001200341700001300353700001800366700001200384700001500396700002000411245020900431856007500640300001100715490000700726520191900733022001402652       2026                            d  c09/202610aRifampicin10aClarithromycin10aBuruli ulcer10arandomized controlled trial10aGhana1 aAgbanyo A1 aAmoako Y1 aOpondo C1 aOppong M1 aAsante-Poku A1 aNovignon J1 aTuffour J1 aMintah I1 aTuwor R1 aAhiatrogah D1 aAkuffo R1 aGborglah M1 aMosweu I1 aPitt C1 aAllen E1 aWalker S1 aYeboah-Manu D1 aMarks M1 aPhillips R1 acollaboration S00aHigh-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.  uhttps://pmc.ncbi.nlm.nih.gov/articles/PMC13645219/pdf/pntd.0014783.pdf  a1 - 140 v203 a<p><strong>BACKGROUND: </strong></p>

<p>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.</p>

<p><strong>METHODOLOGY: </strong></p>

<p>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.</p>

<p><strong>FINDINGS: </strong></p>

<p>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.</p>

<p><strong>CONCLUSION: </strong></p>

<p>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.</p>
  a1935-2735