Clinical Trial: BURULICO Drug Trial Study Protocol: RCT SR8/SR4+CR4, GHANA

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomised Trial for Early Lesions Caused by M. Ulcerans - Comparison Between 8 Weeks Streptomycin and Rifampicin (SR), or 4 Weeks SR Followed by 4 Weeks R Plus Clarithromycin

Brief Summary:

The standard for treatment Buruli ulcer disease (BUD) used to be surgery but the WHO now advises streptomycin (S, 15 mg/kg daily, intramuscularly) and rifampicin (R,10 mg/kg daily) along with surgery. This preliminary advice was based on observations in 21 patients with pre-ulcerative lesions of BUD, who were given daily SR treatment for varying periods of time. In patients treated with SR for at least 4 weeks, M. ulcerans could no longer be cultured from excised lesions. SR has been introduced without a formal evaluation or comparison with other treatments have been conducted or published, but the impression is that this treatment is beneficial and may cure BUD without additional surgical management.

This study protocol evaluated the hypothesis that early, limited lesions of BUD(pre-ulcerative or ulcerated lesions, ≤ 10 cm maximum diameter), can be healed without recurrence using antimycobacterial drug therapy, without the need for debridement surgery.

In endemic regions in Ghana, patients will be actively recruited and followed if ≥ 5 years of age, and with early (i.e., onset < 6 months) BUD.

  • consent by patients and / or care givers / legal representatives
  • clinical evaluation, and by
  • analysis of three 0.3 cm punch biopsies under local anaesthesia.
  • disease confirmation: dry reagent-based polymerase chain reaction (DRB-PCR IS2404)
  • randomization: either SR for 8 weeks, or 4 weeks of SR followed by R and clarithromycin (C)
  • stratification: ulcerative or pre-ulcerative lesions.

Biopsies processed for his

Detailed Summary:

Buruli ulcer disease (BUD) is caused by infection with Mycobacterium ulcerans. It usually starts as a small nodule under the skin but may progress to an ulcerative lesion; and eventually large, usually painless ulcers may develop. When it heals - with surgery or without - it may cause severe scarring resulting in disability and deformity. BUD has emerged as an important infectious disease among rural populations in West Africa. The standard treatment used to be surgical excision for all forms and stages. In 2004. The World Health Organisation advised the use of streptomycin (S, 15 mg/kg daily, intramuscularly) and rifampicin (R,10 mg/kg daily) along with surgery. This preliminary advice was based on the observation in 21 patients with pre-ulcerative lesions of BUD, who were given daily SR treatment for varying periods of time. If patients had received such treatment for at least 4 weeks, M. ulcerans could not be cultured again from the lesions that were excised. The treatment has been implemented in areas with poor access to surgical facilities, in Pobe, Benin, and although no formal evaluation or comparison with other treatments have been conducted or published, the impression is that this treatment is probably beneficial and may cure BUD without the need for additional surgical management.

This study protocol was designed to evaluate the hypothesis that early, limited lesions of Buruli ulcer (M. ulcerans disease; pre-ulcerative or ulcerated lesions, less than or equal to 10 maximum diameter), can be healed without recurrence using antimycobacterial drug therapy, without the need for debridement surgery.

In endemic regions in Ghana, active case finding will be followed by accrual of patients

  • 5 years of age and over, with
  • reduction in lesion surface area and/or clinically assessed improvement on completion of treatment, averting the need for debridement surgery [ Time Frame: during treatment and follow-up x 12 months ]
  • adverse events [ Time Frame: during treatment and follow-up x 12 months ]
  • functional limitations [ Time Frame: at end of follow-up (12 months) ]


Original Secondary Outcome: reduction in lesion surface area and/or clinically assessed improvement on completion of treatment, averting the need for debridement surgery

Information By: University Medical Center Groningen

Dates:
Date Received: May 2, 2006
Date Started: May 2006
Date Completion:
Last Updated: June 29, 2010
Last Verified: April 2010