Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy
Status:
Recruiting
Trial end date:
2024-11-30
Target enrollment:
Participant gender:
Summary
Buruli ulcer (BU) is a skin Neglected Tropical Disease (NTD) that is caused by Mycobacterium
ulcerans. It affects skin, soft tissues and bones causing long-term morbidity, stigma and
disability. The greatest burden falls on children in sub-Saharan Africa. Treating BU requires
8-weeks with daily rifampicin and clarithromycin, wound care, and sometimes tissue grafting
and surgery. Healing can take up to one year. Compliance is challenging due to socioeconomic
determinants and may pose an unbearable financial burden to the household.
Recent studies led by members of this Consortium demonstrated that beta-lactams combined with
rifampicin and clarithromycin are synergistic against M. ulcerans in vitro.
Amoxicillin/clavulanate is oral, suitable for treatment in adults and children, and readily
available with an established clinical pedigree. Its inclusion in a triple oral BU therapy
has the potential of improving healing and shortening BU therapy.
The investigators propose a single blinded, randomized, controlled open label non-inferiority
phase II, multi-centre trial in Benin with participants stratified according to BU category
lesions and randomized in two oral regimens: (i) Standard [RC8]: rifampicin plus
clarithromycin (RC) therapy for 8 weeks; and (ii) Investigational [RCA4]: standard (RC) plus
amoxicillin/clavulanate (A) for 4 weeks. At least, a total of 140 patients will be recruited
(70 per treatment arm), of which at least 132 will be PCR-confirmed. The primary efficacy
outcome will be lesion healing without recurrence and without excision surgery 12 months
after start of treatment (i.e. cure). A clinical expert panel assessing the need of excision
surgery in both treatment arms will be blinded for treatment allocation in order to make
objectives comparisons. Decision for excision surgery will be delayed to 14 weeks after
initiation of antibiotic treatment. Secondary clinical efficacy outcomes include recurrence,
treatment discontinuation and compliance rates, and the incidence of adverse effects, among
others. In addition, two sub-studies will be performed: a pharmacokinetic (PK) analysis and a
bacterial clearance study.
If successful, this study will create a new paradigm for BU treatment, which could inform
changes in WHO policy and practice. This trial may also provide information on treatment
shortening strategies for other mycobacterial infections, such as tuberculosis or leprosy.
Phase:
Phase 2
Details
Lead Sponsor:
Fundacion Agencia Aragonesa para la Investigacion y Desarrollo (ARAID)
Collaborators:
Fondation Raoul Follereau Fundación Anesvad Instituto de Salud Carlos III Universidad de Zaragoza Université d'Abomey-Calavi