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

This study has been completed.
Sponsor:
Information provided by:
University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00321178
First received: May 2, 2006
Last updated: June 29, 2010
Last verified: April 2010
  Purpose

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 histopathology, DRB-PCR-, microscopy, culture, genomic, and sensitivity tests. Lesions assessed regularly for progression or healing during treatment. Drug toxicity monitoring included blood cell counts, liver enzymes and renal tests; and ECG and audiographic tests.

Primary endpoint: healing without recurrence at 12 months follow-up after start of treatment Secondary endpoint: reduction in lesion surface area and/or clinically assessed improvement on completion of treatment, averting the need for debridement surgery.

Recurrences biopsied for confirmation, using PCR, histopathology, and culture. Sample size calculation: 2x74 fully evaluable patients; 80% power to detect a difference of 20 % in recurrence-free cure 12 months after start of treatment between the two groups (60 versus 80%). A Data Safety and Monitoring Board made interim analysis assessments.


Condition Intervention Phase
Buruli Ulcer
Mycobacterium Ulcerans
Drug: SR4 - switch to CR4
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • healing without recurrence and without debridement surgery at 12 months follow-up after start of treatment [ Time Frame: 12 months follow-up after start of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • adverse events [ Time Frame: during treatment and follow-up x 12 months ] [ Designated as safety issue: Yes ]
  • functional limitations [ Time Frame: at end of follow-up (12 months) ] [ Designated as safety issue: Yes ]

Enrollment: 151
Study Start Date: May 2006
Study Completion Date: February 2009
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SR4/CR4
after 4 weeks of standard treatment with streptomycin and rifampicin, patients in the experimental arm switch to oral treatment consisting of rifampicin and clarithromycin
Drug: SR4 - switch to CR4
switch to oral treatment after 4 weeks SR 'standard' therapy
Other Name: clarithromycin: Clacid
Active Comparator: SR8
standard treatment consisting of 8 weeks of streptomycin and rifampicin
Drug: SR4 - switch to CR4
switch to oral treatment after 4 weeks SR 'standard' therapy
Other Name: clarithromycin: Clacid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients
  • At least 5 years of age
  • A clinical diagnosis of early M. ulcerans disease including:

    • Nodules
    • Plaques and small ulcers with or without oedema and less than or equal to 10cm in maximum diameter
    • Disease duration no longer than six months
    • DRB-PCR positive for M. ulcerans

Exclusion Criteria:

  • Treatment with macrolide or quinolone antibiotics, or antituberculous medication, or immunomodulatory drugs including corticosteroids within the previous one month.
  • Current treatment with any drugs likely to interact with the study medication, e.g, anticoagulants, cyclosporin, phenytoin, oral contraceptive, and phenobarbitone.
  • History of hypersensitivity to rifampicin, streptomycin and or clarithromycin.
  • History or having current clinical signs of ascites, jaundice, partial or complete deafness, myasthenia gravis, renal dysfunction (known or suspected), diabetes mellitus, and immune compromise; or evidence for past or present tuberculosis.
  • Pregnancy
  • Inability to take oral medication or having gastrointestinal disease likely to interfere with drug absorption.
  • Excessive alcohol intake.
  • Any situation or condition which may compromise ability to comply with the trial procedures.
  • Lack of willingness to give informed consent (and/or assent by parent/legal representative).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00321178

Locations
Ghana
Agogo Hospital
Agogo, Ashanti Region, Ghana
Nkawie-Toaso Hospital
Nkawie, Ashanti Region, Ghana
Sponsors and Collaborators
University Medical Centre Groningen
Investigators
Principal Investigator: Tjip S van der Werf, MD PhD University Medical Centre Groningen, University of Groningen, the Netherlands
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof TS van der Werf, UMCG, University of Groningen, the Netherlands
ClinicalTrials.gov Identifier: NCT00321178     History of Changes
Other Study ID Numbers: BURULICODRUGTRIAL, EU FP6 2003-INCO-Dev2-015476
Study First Received: May 2, 2006
Last Updated: June 29, 2010
Health Authority: Ghana: Ministry of Health

Keywords provided by University Medical Centre Groningen:
Mycobacterium ulcerans
Buruli ulcer
Ghana
randomized comparison
streptomycin
rifampicin
clarithromycin

Additional relevant MeSH terms:
Mycobacterium Infections
Ulcer
Buruli Ulcer
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Pathologic Processes
Mycobacterium Infections, Nontuberculous
Skin Ulcer
Skin Diseases
Rifampin
Streptomycin
Clarithromycin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014