A Phase 2/3 interventional study of Clarithromycin Extended Release and Streptomycin intramuscular injection in Mycobacterium Ulcerans Infection, sponsored by University Medical Center Groningen. Completed at 5 sites in 2 countries. Open to participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2019-09-26.
Sponsored by University Medical Center Groningen · Phase 2/3, Interventional, and Treatment
This is a WHO-sponsored trial.
Combination therapy with streptomycin and rifampicin has been the standard antibiotic treatment for M. ulcerans infection since 2004. In March 2010, a WHO Technical Advisory Group recommended that a trial be carried out to develop a fully oral treatment for the disease. Although the current treatment is effective, injection with streptomycin is a problem. Several small observational studies (published and unpublished) have shown that a fully oral treatment is promising.
This WHO sponsored study will be a randomized, controlled open label non-inferiority phase II/III, multi-centre trial (1 centre in Benin and 4 centres in Ghana), with two parallel treatment groups. The ultimate goal is to search for an effective alternative treatment to the current standard WHO-recommended therapy for all forms of Buruli ulcer, which includes injections of streptomycin with inherent logistic, operational and safety disadvantages.
Financial and material support:
A total of 415 patients in whom Buruli ulcer has been clinically diagnosed will be included in the study, which will consist of 332 cases of category I and II Buruli ulcers (\<10 cm) confirmed by polymerase chain reaction (PCR), plus 83 non PCR-confirmed Buruli ulcers. Patients will be randomized to receive treatment with the two antibiotic regimens as follows:
(i) Regimen I (SR8): 15 mg/kg streptomycin per day intramuscular injection for 8 weeks plus 10 mg/kg per day oral rifampicin for 8 weeks; (ii) Regimen II (CR8): 15 mg/kg per day oral extended-release clarithromycin for 8 weeks plus 10 mg/kg per day oral rifampicin for 8 weeks.
Assessments before, during and after the course of antibiotic treatment will include full medical history, clinical assessments and monitoring of vital signs, assessment of the lesion, laboratory investigations, hearing test, electrocardiogram, pregnancy test, voluntary HIV counseling and testing, and functional limitation assessment. The primary efficacy parameters are healing without recurrence and without excision surgery 12 months after the start of treatment.
The primary endpoint will be assessed by a panel of experts unaware of the treatment ('single blinded' for treatment allocation).
Statistician:
Mr Bruno Scherrer, Consultant, Drugs for Neglected Diseases initiative, Switzerland
Data Management:
Mr Raymond Omollo, Drugs for Neglected Diseases initiative (DNDi) Africa
University Medical Center Groningen is the lead sponsor of 627 studies on the registry; 176 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Streptomycin (S: 15 mg/kg per day, intramuscularly) in combination with rifampicin (R: 10 mg/kg per day, orally) for 8 weeks
Drug: Streptomycin intramuscular injection
Clarithromycin (C: 15 mg/kg per day, oral extended release formulation) in combination with rifampicin (10 mg/kg per day, orally) for 8 weeks
Drug: Clarithromycin Extended Release
oral administration of Clarithromycin extended release
daily intramuscular drug injection
healing without recurrence and without excision surgery
complete epithelialisation and absence of swelling at the site of original infection, measured 12 months after start of treatment; lesion site will be examined by inspection and palpation, and documented by digital camera; digital images will be examined by panel of wound experts unaware of treatment allocation
Time frame: 12 months after start of treatment
Recurrence rate within 12 months of treatment initiation
number of recurrent lesions occurring after initial healing within 12 months after start of treatment
Time frame: 12 months
Rate of treatment failure within 12 months of treatment initiation
proportion of treatment failure will be compared between groups
Time frame: 12 months
Rate of paradoxical response within 12 months of treatment initiation
paradoxical responses that have occurred during BUD treatment will be compared in both treatment arms
Time frame: 12 months
Proportion of patients with reduction in lesion surface area within 12 months of treatment initiation
if not cured, will there be a difference between groups in terms of reduction of lesion size?
Time frame: 12 months
Time taken for complete lesion healing within 12 months of treatment initiation
do lesions heal faster in one of the two treatments?
Time frame: 12 months
Proportion (%) of patients with complete healing without additional surgery or relapse
Time frame: 12 months
Interval between healing and recurrence
if recurrences occur, there might be a difference in time between healing and recurrences between treatment groups
Time frame: 12 months
Proportion of each type of surgery within 12 months of treatment initiation
We do not expect surgery but IF doctors operate, which type of surgery would doctors use, and does this differ between groups?
Time frame: 12 months
Time from treatment initiation to surgery if any
does the timing of surgery differ between groups for the proportion of patients in whom doctors decide to operate?
Time frame: 12months
Proportion of patients with residual functional limitations
do treatments differ in terms of chance to develop functional limitations?
Time frame: 12 months
Treatment discontinuation and compliance rates
one treatment might be better tolerated than the other; do treatments differ in terms of adherence problems, and do participants in any of these two treatment arms differ in terms of the chance to discontinue the treatment?
Time frame: 8 weeks
Incidence of all adverse effects (AEs) within 12 months of treatment initiation
adverse effects occurring during or after treatment may be different between treatments
Time frame: 12 months
Plan to share: Yes — after publication, IPD will be made available at the time of publication; enrollment is complewted with 310 participants enrolled by Dec 2017; final report submitted for publication Sept 2019
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: data analysis report as well as data in OpenClinica deposited with DNDi Regional Africa Office Nairobi
This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Clarithromycin
Buruli Ulcer
University Medical Center Groningen →