Shortening Buruli ulcer treatment: the BLMs4BU clinical trial
Researcher:
Ramón García, Santiago
Congress:
TUBERCULOSIS 2022 - EMBO Workshop on Tuberculosis 2022 - From innovation to intervention
Participation type:
Póster
Other authors:
R.C. Johnson, R.O. Phillips, N.K. Kotey, M. Kaloga, D. Gadah, M. Tchalim, J. Addo, G. Díez, I. Cruz, E. Saez-López, S. Ramón García
Year:
2022
Location:
Paris, France. Sep 12-16 2022
Buruli ulcer (BU) is a neglected tropical skin disease, caused by Mycobacterium ulcerans (Mul), that affects mainly children under the age of 15 years in Africa. Current WHO-recommended treatment requires 8-weeks of daily rifampicin and clarithromycin, wound care and, sometimes, tissue grafting and surgery. Healing can take up to one year and may pose an unbearable financial burden to the household. Recent repurposing studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic in vitro against Mul (PMID: 30689630) leading to the hypothesis that the inclusion of amoxicillin/clavulanate may improve and shorten BU therapy.
The aim of the BLMs4BU clinical trial is to evaluate whether co-administration of amoxicillin/clavulanate with rifampicin/clarithromycin can shorten BU treatment from 8 to 4 weeks. A randomized, controlled open label non-inferiority Phase II, multi-centre trial started in Benin in December 2021 (ClinicalTrials.gov Identifier: NCT05169554). A Phase III multi- centre trial in Ghana, Togo and Côte d’Ivoire is planned to start in December 2022. Patients are stratified according to BU category lesions and randomized to two regimens: (i) standard: rifampicin/clarithromycin (RC) for 8 weeks; and (ii) investigational: standard RC plus amoxicillin/clavulanate for 4 weeks. Patients will be followed-up for 12 months and managed according to standard clinical procedures. Decision for excision surgery will be made at week 14 after treatment initiation by an independent clinical expert panel. The primary efficacy outcome is cure (i.e., lesion healing without recurrence) without excision surgery 12 months after start of treatment.
If successful, this study will create a new paradigm for BU treatment, which could lead to a change in WHO policy and practice for this disease. A shorter, highly effective, all-oral treatment will improve the care of BU patients, adherence to treatment and will lead to a decrease in direct and indirect costs. This trial may also provide information on treatment shortening strategies for other mycobacterial infections, such as tuberculosis or leprosy, where rifampicin is the cornerstone drug.
This trial is funded by grants from the Tres Cantos Open Lab Foundation and the Anesvad Foundation.
Buruli ulcer (BU) is a neglected tropical skin disease, caused by Mycobacterium ulcerans (Mul), that affects mainly children under the age of 15 years in Africa. Current WHO-recommended treatment requires 8-weeks of daily rifampicin and clarithromycin, wound care and, sometimes, tissue grafting and surgery. Healing can take up to one year and may pose an unbearable financial burden to the household. Recent repurposing studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic in vitro against Mul (PMID: 30689630) leading to the hypothesis that the inclusion of amoxicillin/clavulanate may improve and shorten BU therapy.
The aim of the BLMs4BU clinical trial is to evaluate whether co-administration of amoxicillin/clavulanate with rifampicin/clarithromycin can shorten BU treatment from 8 to 4 weeks. A randomized, controlled open label non-inferiority Phase II, multi-centre trial started in Benin in December 2021 (ClinicalTrials.gov Identifier: NCT05169554). A Phase III multi- centre trial in Ghana, Togo and Côte d’Ivoire is planned to start in December 2022. Patients are stratified according to BU category lesions and randomized to two regimens: (i) standard: rifampicin/clarithromycin (RC) for 8 weeks; and (ii) investigational: standard RC plus amoxicillin/clavulanate for 4 weeks. Patients will be followed-up for 12 months and managed according to standard clinical procedures. Decision for excision surgery will be made at week 14 after treatment initiation by an independent clinical expert panel. The primary efficacy outcome is cure (i.e., lesion healing without recurrence) without excision surgery 12 months after start of treatment.
If successful, this study will create a new paradigm for BU treatment, which could lead to a change in WHO policy and practice for this disease. A shorter, highly effective, all-oral treatment will improve the care of BU patients, adherence to treatment and will lead to a decrease in direct and indirect costs. This trial may also provide information on treatment shortening strategies for other mycobacterial infections, such as tuberculosis or leprosy, where rifampicin is the cornerstone drug.
This trial is funded by grants from the Tres Cantos Open Lab Foundation and the Anesvad Foundation.