Timing of Surgical Intervention in Buruli Ulcer Patients Treated With Antibiotics (Burulitime)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by University Medical Centre Groningen.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
PNLUB, Ministère de la santé, Cotonou, République du Bénin.
Laboratoire de Référence des Mycobactéries (LRM) Cotonou
Information provided by (Responsible Party):
Ymkje Stienstra, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01432925
First received: September 8, 2011
Last updated: July 13, 2012
Last verified: July 2012
  Purpose

SUMMARY

Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Observation of Buruli ulcer lesions of limited size during antibiotic treatment showed that during treatment there is a paradoxical increase of the lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide whether surgery is needed four weeks after the start of antibiotics. This might be too early in the healing process. The investigators hypothesize that delay in surgery is safe, and that it results in a reduction of the number of surgical interventions.

Objectives:

Primary Objective of this study is to compare the need for surgical treatment in standard timing of surgery at the end of eight weeks antimicrobial treatment with a policy to postpone surgical treatment until week 14.

Secondary Objectives are to study whether postponing surgery leads to less extensive surgery and a change in frequency of functional limitations;

Study design:

Patients will be randomized for surgery at week 8 after start of antibiotic treatment and week 14 after start of treatment. Reasons for treating doctors to decide to intervene with surgery will be according to current clinical practice and will be clearly defined in this protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All patients will be followed and lesional size using acetate sheet recordings will be used during follow-up.

Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin. Patients who are pregnant, have a contraindication for general anaesthesia and children below three years old will be excluded. 130 Patients in each treatment arm will be included to detect a difference in percentage of patients needing surgery of 20 percent.

Main study parameters/endpoints: Primary outcome measure is the number of patients healed without surgery. Secondary outcome measures are the extent of surgery by measurement of lesional size, functional limitations after the end of treatment and one year after the start of treatment and the duration of admission.


Condition Intervention
Mycobacterium Ulcerans Disease
Buruli Ulcer
Procedure: surgical intervention on Buruli ulcer

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Timing of the Decision on Surgical Intervention for Buruli Ulcer Patients Treated With Rifampicin/Streptomycin

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Healing without surgical intervention [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 260
Study Start Date: September 2011
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
evaluation surgical intervention at week 8 Procedure: surgical intervention on Buruli ulcer
Can the need for surgical intervention be avoided by delay of the decision on surgical intervention, comparing the need on surgical intervention from time points of week 8 and week 14 (number of weeks after start of antibiotic treatment with streptomycin/rifampicin).
evaluation surgical intervention at week 14 Procedure: surgical intervention on Buruli ulcer
Can the need for surgical intervention be avoided by delay of the decision on surgical intervention, comparing the need on surgical intervention from time points of week 8 and week 14 (number of weeks after start of antibiotic treatment with streptomycin/rifampicin).

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a clinical picture of Buruli ulcer disease in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin, will be included at start of antibiotic treatment.
  • All stages of the disease will be included. Only patients with confirmed disease by direct microscopy following acid-fast staining or PCR will be included.

Exclusion Criteria:

  • Patients not on the standard treatment of eight weeks of rifampicin and streptomycin for any reason, will be excluded from this study.
  • Treatment with macrolide or quinolone antibiotics, or antituberculous medication, or immune-modulatory drugs including corticosteroids within the previous one month.
  • Patients not compliant with the antibiotic therapy will be excluded as well. Non-compliance is defined as the use of < 70 % of the prescribed antibiotics.
  • Patients with a contraindication for general anaesthesia are not able to participate.
  • Pregnancy.
  • Osteomyelitis.
  • Lesion close to the eye, with preferred standard treatment to wait for effect antibiotic treatment on extent surgery.
  • The BUFLS (Buruli ulcer functional limitation score) cannot be applied to children below three years and therefore will not participate.
  • Patients reporting to refuse surgery at any point in the intended treatment, cannot be included.
  • Any situation or condition which may compromise ability to comply with the trial procedures.
  • Patients known to be HIV positive.
  • 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: NCT01432925

Contacts
Contact: Ymkje Stienstra, MD PhD +31-50-3616161 ext 44764 y.stienstra@umcg.nl
Contact: Yves Barogui, MD yvesbaro@yahoo.fr

Locations
Benin
Buruli ulcer center Allada Recruiting
Allada, Benin
Contact: G Sopoh, MD PhD       ghislainsop@yahoo.fr   
Buruli ulcer center Lalo Recruiting
Lalo, Benin
Contact: Y Barogui, MD       yvesbaro@yahoo.fr   
Sponsors and Collaborators
University Medical Centre Groningen
PNLUB, Ministère de la santé, Cotonou, République du Bénin.
Laboratoire de Référence des Mycobactéries (LRM) Cotonou
Investigators
Principal Investigator: D Agossadou, MD Program national lutte contre la lèpre et l'ulcère de Buruli, ministère de la santé, Hospital Lalo
Principal Investigator: G Sopoh, MD PhD Program national lutte contre la lèpre et l'ulcère de Buruli, Ministère de la Santé, Cotonou, Bénin, hospital Allada
Principal Investigator: Tjip S van der Werf, MD PhD UMCG - internal medicine/infectious diseases
Principal Investigator: R OC Johnson, MD PhD Cotonou, Bénin
  More Information

No publications provided

Responsible Party: Ymkje Stienstra, MD PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01432925     History of Changes
Other Study ID Numbers: BURULIVENI
Study First Received: September 8, 2011
Last Updated: July 13, 2012
Health Authority: Bénin: COMITE NATIONAL PROVISOIRE D'ETHIQUE DE LA RECHERCHE EN SANTE

Keywords provided by University Medical Centre Groningen:
Buruli ulcer
Mycobacterium ulcerans
Streptomycin
Rifampicin
Functional limitations
surgery
Bénin

Additional relevant MeSH terms:
Mycobacterium Infections
Mycobacterium Infections, Nontuberculous
Ulcer
Buruli Ulcer
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Pathologic Processes
Skin Ulcer
Skin Diseases
Anti-Bacterial Agents
Rifampin
Streptomycin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antitubercular
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 19, 2014