2026-04-27T01:59:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/152932025-06-18T12:52:13Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608col_20.500.12105_19613

00925njm 22002777a 4500 dc Johnson, Roch Christian author Sáez-López, Emma author Anagonou, Esaï Sèdjro author Kpoton, Godwin Gérard author Ayelo, Adjimon Gilbert author Gnimavo, Ronald Sètondji author Mignanwande, Franck Zinsou author Houezo, Jean-Gabin author Sopoh, Ghislain Emmanuel author Addo, Juliet author Orford, Lindsay author Vlasakakis, Georgios author Biswas, Nandita author Calderon, Felix author Della Pasqua, Oscar author Gine-March, Anna author Herrador, Zaida author Mendoza-Losana, Alfonso author Díez, Gabriel author Cruz, Israel author Ramón-García, Santiago author 2022-07-08 Background: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. Methods: We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. Discussion: If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections). Trials. 2022 Jul 8;23(1):559. http://hdl.handle.net/20.500.12105/15293 35804454 10.1186/s13063-022-06473-9 1745-6215 Trials Buruli ulcer Skin neglected tropical disease Treatment shortening Non-inferiority Drug combination Amoxicillin Clavulanate Pharmacokinetics Bacterial clearance Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin