Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00321178
Status:
COMPLETED
Last Update Posted:
2010-06-30
First Post:
2006-05-02
Brief Title:
BURULICO Drug Trial Study Protocol RCT SR8SR4CR4 GHANA
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2010-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BURULICO
Brief Summary:
The standard for treatment Buruli ulcer disease BUD used to be surgery but the WHO now advises streptomycin S 15 mgkg daily intramuscularly and rifampicin R10 mgkg 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 BUDpre-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 ie onset 6 months BUD
consent by patients and or care givers legal representatives
clinical evaluation and by
analysis of three 03 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 andor 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
This study protocol evaluated the hypothesis that early limited lesions of BUDpre-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 ie onset 6 months BUD
consent by patients and or care givers legal representatives
clinical evaluation and by
analysis of three 03 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 andor 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
Detailed Description:
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 mgkg daily intramuscularly and rifampicin R10 mgkg 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
limited early ie onset less than 6 months lesions of Buruli ulcer
After appropriate consent by patients and or their care givers or legal representatives patients will be diagnosed both by
clinical evaluation and
by analysis of three punch biopsies 03 cm each under local anaesthesia
Only patients with confirmation of M ulcerans disease - presence of dry reagent-based polymerase chain reaction DRB-PCR signal with insertion sequence IS2404 were to be randomised to receive either SR for 8 weeks or 4 weeks of SR followed by oral treatment consisting of R and clarithromycin C as allocated by a computer-generated program patients will be stratified for ulcerative or pre-ulcerative lesions
Patients who meet the clinical criteria for M ulcerans disease but are PCR negative will be offered 8 weeks RS treatment as is presently provisionally recommended by WHO and will be evaluated separately according to the protocol for patients allocated to 8 weeks RS treatment All biopsies from lesions will be subjected to histopathology DRB-PCR- microscopy culture genomic sensitivity tests and external quality control in laboratories in Kumasi KNUST Hamburg BNITM Munich DITM and Antwerp ITM Lesions will be assessed regularly for progression or healing during treatment Drug toxicity will likewise be monitored renal and audiographic tests for S and C ECG for C and liver enzymes for R and C and blood cell counts for C
The primary endpoint is healing without recurrence at 12 months follow-up after start of treatment Secondary endpoint is reduction in lesion surface area andor clinically assessed improvement on completion of treatment averting the need for debridement surgery
Recurrences will be biopsied for confirmation using PCR histopathology and culture In all 200 patients will need to be screened according to protocol and 2x74 evaluable patients will be randomised based on a power analysis 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 will make interim analyses
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
limited early ie onset less than 6 months lesions of Buruli ulcer
After appropriate consent by patients and or their care givers or legal representatives patients will be diagnosed both by
clinical evaluation and
by analysis of three punch biopsies 03 cm each under local anaesthesia
Only patients with confirmation of M ulcerans disease - presence of dry reagent-based polymerase chain reaction DRB-PCR signal with insertion sequence IS2404 were to be randomised to receive either SR for 8 weeks or 4 weeks of SR followed by oral treatment consisting of R and clarithromycin C as allocated by a computer-generated program patients will be stratified for ulcerative or pre-ulcerative lesions
Patients who meet the clinical criteria for M ulcerans disease but are PCR negative will be offered 8 weeks RS treatment as is presently provisionally recommended by WHO and will be evaluated separately according to the protocol for patients allocated to 8 weeks RS treatment All biopsies from lesions will be subjected to histopathology DRB-PCR- microscopy culture genomic sensitivity tests and external quality control in laboratories in Kumasi KNUST Hamburg BNITM Munich DITM and Antwerp ITM Lesions will be assessed regularly for progression or healing during treatment Drug toxicity will likewise be monitored renal and audiographic tests for S and C ECG for C and liver enzymes for R and C and blood cell counts for C
The primary endpoint is healing without recurrence at 12 months follow-up after start of treatment Secondary endpoint is reduction in lesion surface area andor clinically assessed improvement on completion of treatment averting the need for debridement surgery
Recurrences will be biopsied for confirmation using PCR histopathology and culture In all 200 patients will need to be screened according to protocol and 2x74 evaluable patients will be randomised based on a power analysis 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 will make interim analyses
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EU FP6 2003-INCO-Dev2-015476 | None | None | None |