Randomized Controlled Trial Comparing Efficacy of 8 Weeks Treatment With Clarithromycin and Rifampicin Versus Streptomycin and Rifampicin for Buruli Ulcer (M. Ulcerans Infection)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 310
- 试验地点
- 5
- 主要终点
- healing without recurrence and without excision surgery
研究概览
简要总结
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 Several small observational studies (published and unpublished) have shown that a fully oral treatment is promising.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:
- American Leprosy Missions, USA
- Raoul Follereau Foundation, France
- MAP International, USA
- Sanofi, France
- 7th Framework Programme of the European Union: BuruliVac project (241500)
- Aranz Medical Limited, New Zealand
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SR8
Streptomycin (S: 15 mg/kg per day, intramuscularly) in combination with rifampicin (R: 10 mg/kg per day, orally) for 8 weeks
干预措施: Streptomycin intramuscular injection (Drug)
CR8
Clarithromycin (C: 15 mg/kg per day, oral extended release formulation) in combination with rifampicin (10 mg/kg per day, orally) for 8 weeks
干预措施: Clarithromycin Extended Release (Drug)
结局指标
主要结局
healing without recurrence and without excision surgery
时间窗: 12 months after start of treatment
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
次要结局
- Rate of treatment failure within 12 months of treatment initiation(12 months)
- Proportion of patients with reduction in lesion surface area within 12 months of treatment initiation(12 months)
- Rate of paradoxical response within 12 months of treatment initiation(12 months)
- Proportion (%) of patients with complete healing without additional surgery or relapse(12 months)
- Interval between healing and recurrence(12 months)
- Time from treatment initiation to surgery if any(12months)
- Proportion of each type of surgery within 12 months of treatment initiation(12 months)
- Proportion of patients with residual functional limitations(12 months)
- Recurrence rate within 12 months of treatment initiation(12 months)
- Time taken for complete lesion healing within 12 months of treatment initiation(12 months)
- Treatment discontinuation and compliance rates(8 weeks)
- Incidence of all adverse effects (AEs) within 12 months of treatment initiation(12 months)
研究者
Tjip van der Werf
Professor
University Medical Center Groningen