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Trial record 2 of 2 for:    "Buruli Ulcer" | "Clarithromycin"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00321178
Recruitment Status : Completed
First Posted : May 3, 2006
Last Update Posted : June 30, 2010
Information provided by:
University Medical Center Groningen

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 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 or disease Intervention/treatment Phase
Buruli Ulcer Mycobacterium Ulcerans Drug: SR4 - switch to CR4 Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2006
Actual Primary Completion Date : January 2008
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. adverse events [ Time Frame: during treatment and follow-up x 12 months ]
  3. functional limitations [ Time Frame: at end of follow-up (12 months) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00321178

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

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Prof TS van der Werf, UMCG, University of Groningen, the Netherlands Identifier: NCT00321178     History of Changes
EU FP6 2003-INCO-Dev2-015476
First Posted: May 3, 2006    Key Record Dates
Last Update Posted: June 30, 2010
Last Verified: April 2010
Keywords provided by University Medical Center Groningen:
Mycobacterium ulcerans
Buruli ulcer
randomized comparison
Additional relevant MeSH terms:
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Buruli Ulcer
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Nontuberculous
Skin Ulcer
Skin Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers