000119015 001__ 119015 000119015 005__ 20240319081026.0 000119015 0247_ $$2doi$$a10.1186/s13063-022-06473-9 000119015 0248_ $$2sideral$$a130306 000119015 037__ $$aART-2022-130306 000119015 041__ $$aeng 000119015 100__ $$aJohnson, Roch Christian 000119015 245__ $$aComparison 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 000119015 260__ $$c2022 000119015 5060_ $$aAccess copy available to the general public$$fUnrestricted 000119015 5203_ $$aBackground 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). 000119015 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000119015 590__ $$a2.5$$b2022 000119015 592__ $$a0.814$$b2022 000119015 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b99 / 136 = 0.728$$c2022$$dQ3$$eT3 000119015 593__ $$aPharmacology (medical)$$c2022$$dQ2 000119015 593__ $$aMedicine (miscellaneous)$$c2022$$dQ2 000119015 594__ $$a3.6$$b2022 000119015 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000119015 700__ $$aSáez-López, Emma$$uUniversidad de Zaragoza 000119015 700__ $$aAnagonou, Esaï Sèdjro 000119015 700__ $$aKpoton, Godwin Gérard 000119015 700__ $$aAyelo, Adjimon Gilbert 000119015 700__ $$aGnimavo, Ronald Sètondji 000119015 700__ $$aMignanwande, Franck Zinsou 000119015 700__ $$aHouezo, Jean-Gabin 000119015 700__ $$aSopoh, Ghislain Emmanuel 000119015 700__ $$aAddo, Juliet 000119015 700__ $$aOrford, Lindsay 000119015 700__ $$aVlasakakis, Georgios 000119015 700__ $$aBiswas, Nandita 000119015 700__ $$aCalderon, Felix 000119015 700__ $$aDella Pasqua, Oscar 000119015 700__ $$aGine-March, Anna 000119015 700__ $$aHerrador, Zaida 000119015 700__ $$aMendoza-Losana, Alfonso 000119015 700__ $$aDíez, Gabriel 000119015 700__ $$aCruz, Israel 000119015 700__ $$0(orcid)0000-0002-8480-0325$$aRamón-García, Santiago 000119015 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000119015 773__ $$g23 (2022), 559 [17 pp.]$$pTrials$$tTrials$$x1745-6215 000119015 8564_ $$s2459485$$uhttps://zaguan.unizar.es/record/119015/files/texto_completo.pdf$$yVersión publicada 000119015 8564_ $$s2192969$$uhttps://zaguan.unizar.es/record/119015/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000119015 909CO $$ooai:zaguan.unizar.es:119015$$particulos$$pdriver 000119015 951__ $$a2024-03-18-16:46:11 000119015 980__ $$aARTICLE