NCT01659437

WHO Drug Study for Buruli Ulcer - Comparison of SR8 and CR8

Randomized Controlled Trial Comparing Efficacy of 8 Weeks Treatment With Clarithromycin and Rifampicin Versus Streptomycin and Rifampicin for Buruli Ulcer (M. Ulcerans Infection)

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 310 (actual)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: All
• Age: 5 Years
• Healthy volunteers: Not accepted

Summary

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 Several small observational studies (published and unpublished) have shown that a fully oral treatment is promising.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

Detailed description

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

Conditions

• Mycobacterium Ulcerans Infection

Interventions

Type	Name	Description
DRUG	Clarithromycin Extended Release	oral administration of Clarithromycin extended release
DRUG	Streptomycin intramuscular injection	daily intramuscular drug injection

Timeline

• Start date: 2012-12-01
• Primary completion: 2017-12-01
• Completion: 2018-01-01
• First posted: 2012-08-07
• Last updated: 2019-09-26

Locations

5 sites across 2 countries: Benin, Ghana