Mycobacterium Ulcerans Infection Clinical Trial
Official title:
Randomized Controlled Trial Comparing Efficacy of 8 Weeks Treatment With Clarithromycin and Rifampicin Versus Streptomycin and Rifampicin for Buruli Ulcer (M. Ulcerans Infection)
This is a WHO-sponsored trial.
Combination therapy with streptomycin and rifampicin has been the standard antibiotic
treatment for M. ulcerans infection since 2004. In March 2010, a WHO Technical Advisory Group
recommended that a trial be carried out to develop a fully oral treatment for the disease.
Although the current treatment is effective, injection with streptomycin is a problem.
Several small observational studies (published and unpublished) have shown that a fully oral
treatment is promising.
This WHO sponsored study will be a randomized, controlled open label non-inferiority phase
II/III, multi-centre trial (1 centre in Benin and 4 centres in Ghana), with two parallel
treatment groups. The ultimate goal is to search for an effective alternative treatment to
the current standard WHO-recommended therapy for all forms of Buruli ulcer, which includes
injections of streptomycin with inherent logistic, operational and safety disadvantages.
Financial and material support:
1. American Leprosy Missions, USA
2. Raoul Follereau Foundation, France
3. MAP International, USA
4. Sanofi, France
5. 7th Framework Programme of the European Union: BuruliVac project (241500)
6. Aranz Medical Limited, New Zealand
A total of 415 patients in whom Buruli ulcer has been clinically diagnosed will be included
in the study, which will consist of 332 cases of category I and II Buruli ulcers (<10 cm)
confirmed by polymerase chain reaction (PCR), plus 83 non PCR-confirmed Buruli ulcers.
Patients will be randomized to receive treatment with the two antibiotic regimens as follows:
(i) Regimen I (SR8): 15 mg/kg streptomycin per day intramuscular injection for 8 weeks plus
10 mg/kg per day oral rifampicin for 8 weeks; (ii) Regimen II (CR8): 15 mg/kg per day oral
extended-release clarithromycin for 8 weeks plus 10 mg/kg per day oral rifampicin for 8
weeks.
Assessments before, during and after the course of antibiotic treatment will include full
medical history, clinical assessments and monitoring of vital signs, assessment of the
lesion, laboratory investigations, hearing test, electrocardiogram, pregnancy test, voluntary
HIV counseling and testing, and functional limitation assessment. The primary efficacy
parameters are healing without recurrence and without excision surgery 12 months after the
start of treatment.
The primary endpoint will be assessed by a panel of experts unaware of the treatment ('single
blinded' for treatment allocation).
Statistician:
Mr Bruno Scherrer, Consultant, Drugs for Neglected Diseases initiative, Switzerland
Data Management:
Mr Raymond Omollo, Drugs for Neglected Diseases initiative (DNDi) Africa
;