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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Controlled Trial Comparing Efficacy of 8 Weeks Treatment With Clarithromycin and Rifampicin Versus Streptomycin and Rifampicin for Buruli Ulcer (M. Ulcerans Inf

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 Several small observational studies (published and unpublished) have shown that a fully oral treatment is promising.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

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

Sponsor: University Medical Center Groningen

Current Primary Outcome: healing without recurrence and without excision surgery [ Time Frame: 12 months after start of treatment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Recurrence rate within 12 months of treatment initiation [ Time Frame: 12 months ]
  number of recurrent lesions occurring after initial healing within 12 months after start of treatment
• Rate of treatment failure within 12 months of treatment initiation [ Time Frame: 12 months ]
  proportion of treatment failure will be compared between groups
• Rate of paradoxical response within 12 months of treatment initiation [ Time Frame: 12 months ]
  paradoxical responses that have occurred during BUD treatment will be compared in both treatment arms
• Proportion of patients with reduction in lesion surface area within 12 months of treatment initiation [ Time Frame: 12 months ]
  if not cured, will there be a difference between groups in terms of reduction of lesion size?
• Time taken for complete lesion healing within 12 months of treatment initiation [ Time Frame: 12 months ]
  do lesions heal faster in one of the two treatments?
• Proportion (%) of patients with complete healing without additional surgery or relapse [ Time Frame: 12 months ]
• Interval between healing and recurrence [ Time Frame: 12 months ]
  if recurrences occur, there might be a difference in time between healing and recurrences between treatment groups
• Proportion of each type of surgery within 12 months of treatment initiation [ Time Frame: 12 months ]
  We do not expect surgery but IF doctors operate, which type of surgery would doctors use, and does this differ between groups?
• Time from treatment initiation to surgery if any [ Time Frame: 12months ]
  does the timing of surgery differ between groups for the proportion of patients in whom doctors decide to operate?
• Proportion of patients with residual functional limitations [ Time Frame: 12 months ]
  do treatments differ in terms of chance to develop functional limitations?
• Treatment discontinuation and compliance rates [ Time Frame: 8 weeks ]
  one treatment might be better tolerated than the other; do treatments differ in terms of adherence problems, and do participants in any of these two treatment arms differ in terms of the chance to discontinue the treatment?
• Incidence of all adverse effects (AEs) within 12 months of treatment initiation [ Time Frame: 12 months ]
  adverse effects occurring during or after treatment may be different between treatments

Original Secondary Outcome: Same as current

Information By: University Medical Center Groningen

Dates:
Date Received: August 2, 2012
Date Started: December 2012
Date Completion: January 2018
Last Updated: January 21, 2017
Last Verified: January 2017