NCT01659437.

Trial name or title	Randomized controlled trial comparing efficacy of 8 weeks treatment with clarithromycin and rifampicin versus streptomycin and rifampicin for Buruli ulcer (Mycobacterium ulcerans infection)
Methods	Randomized controlled trial (multicentre, open‐label)
Participants	Inclusion criteria: aged 5 years and older, with a clinical diagnosis of BU disease (categories I and II, cross‐sectional diameter ≤ 10 cm) as agreed by study site treatment team led by the lead clinicians Exclusion criteria: lesion sizes > 10 cm in cross‐sectional diameter; children < 5 years, or < 20 kg body weight; pregnancy; previous treatment of Buruli ulcer, tuberculosis, or leprosy with at least 1 of the study drugs (rifampicin, streptomycin, clarithromycin); history of hypersensitivity to rifampicin and/or streptomycin and/or clarithromycin; previous treatment with macrolide or quinolone antibiotics, or antituberculosis medication, or immunomodulatory drugs including corticosteroids within 1 month; current treatment with any drugs likely to interact with the study medication; co‐infection with HIV; history or having current clinical signs of ascites, jaundice, partial or complete deafness, myasthenia gravis, renal dysfunction (known or suspected), diabetes mellitus, and severe immune compromise (for example, immunosuppressive drugs after organ transplant), or evidence of (previous) tuberculosis, Buruli ulcer or leprosy, or terminal illness (for example, metastasized cancer); unable to take oral medication or having gastrointestinal disease likely to interfere with drug absorption; individuals with known or suspected bowel strictures who cannot tolerate macrolide antibiotics such as clarithromycin; mental condition likely to interfere with ability to comply with the study protocol Estimated enrolment: 415
Interventions	Rifampicin (10 mg/kg/d) + streptomycin (15 mg/kg/d), 8 weeks Rifampicin (10 mg/kg/d) + clarithromycin (7.5 mg/kg/d), 8 weeks
Outcomes	Primary outcome Healing without recurrence and without excision surgery (time frame: 12 months after start of treatment) Secondary outcomes Recurrence rate within 12 months of treatment initiation Number of recurrent lesions occurring after initial healing within 12 months of treatment initiation Rate of treatment failure within 12 months of treatment initiation Rate of paradoxical response within 12 months of treatment initiation Proportion of participants with reduction in lesion surface area within 12 months of treatment initiation Time taken for complete lesion healing within 12 months of treatment initiation Proportion (%) of participants with complete healing without additional surgery or relapse Interval between healing and recurrence Proportion of each type of surgery within 12 months of treatment initiation Time from treatment initiation to surgery if any Proportion of participants with residual functional limitations Treatment discontinuation and compliance rates Incidence of all adverse effects within 12 months of treatment initiation
Starting date	December 2012 Anticipated end date: January 2018
Contact information	Tjip S van der Werf, Professor, University Medical Center Groningen (t.s.van.der.werf@umcg.nl)
Notes	Trial location: 1 centre in Benin and 4 centres in Ghana Registration number: NCT01659437

Abbreviations: BU: Buruli ulcer; PCR: polymerase chain reaction