Research Articles >
College of Health Sciences >
Please use this identifier to cite or link to this item:
|Title: ||Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial|
|Authors: ||Phillips, Richard Odame|
Abass, Kabiru Mohamed
Sarfo, Fred Stephen
Gateau, Thierry ...et.al
|Issue Date: ||12-Mar-2020|
|Citation: ||Lancet 2020; 395: 1259–67; https://doi.org/10.1016/ S0140-6736(20)30047-7|
|Abstract: ||Background Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the
skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment
with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly
effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and
tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks
(RC8) with that of RS8 for treatment of early Buruli ulcer lesions.
Methods We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial
comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in
hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were
aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than
10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor
the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full
epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary
endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated
to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437.
Findings Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after
310 participants. Median age of participants was 14 years (IQR 10–29) and 153 (52%) were female. 297 patients had
PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment.
In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%,
91 to 99) of 146 patients in the RC8 group. The difference in proportion, –0·5% (–5·2 to 4·2), was not significantly
greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks.
Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving
RC8. Most adverse events were grade 1–2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended
treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts.
Interpretation Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was
associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for
early, limited lesions of Buruli ulcer.|
|Description: ||An article published in Lancet 2020; 395: 1259–67; https://doi.org/10.1016/ S0140-6736(20)30047-7|
|Appears in Collections:||College of Health Sciences|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.