Phase III Clinical Trial for American Tegumentary Leishmaniasis: Comparison of Standard and Alternative Antimonial Dosage in Patients With American Cutaneous Leishmaniasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Effectiveness of meglumine antimoniate treatment
研究概览
简要总结
"Phase III Clinical Trial for American Tegumentary Leishmaniasis: Comparison of Standard and Alternative Antimonial Dosage in Patients With American Cutaneous Leishmaniasis " has begun in October 2008 at the Laboratory of Leishmaniasis Surveillance at Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, aiming to compare efficacy and safety of the standard recommended schedule with an alternative dosage scheme of meglumine antimoniate in the treatment of American tegumentary leishmaniasis (ATL). It is a study with blind evaluation by the doctors and the responsible for statistical analysis. Patients diagnosed with ATL, eligible for the trial are randomly allocated into one of the schemes with meglumine antimoniate and monitored before, during and after it. There is no single regimen applicable to all forms of leishmaniasis around the world. Therapeutic regimens applied to treat people living in other geographic areas result in mixed outcomes. Ideally, the most appropriate regimens should be established for each endemic area, based on its efficacy, toxicity, difficulties of administration and cost. Given the problems and limitations of the use of pentavalent antimonials (Sb5+) at 20 mg Sb5+ / kg / day, less toxic alternative regimens, i.e. 5mg Sb5+/kg/day, deserve to be better evaluated. The treatment of ATL must heal skin lesions and prevent late mucosal lesion development. The indication of high doses of Sb5+ is based on the evidence that there could be induction of resistance with use of subdoses. However, clinical studies with extended follow-up in Rio de Janeiro have suggested that regular low doses (5mg Sb5+ / kg / day) may constitute an effective scheme, achieving cure rates similar to higher doses, with lower toxicity, ease of implementation and lower cost. Published studies on efficacy and safety of alternative dosage schemes with meglumine antimoniate failed to provide conclusive results so far, for various methodological biases. The need to compare the effectiveness and safety between the standard treatment scheme with meglumine antimoniate currently recommended in Brazil for the treatment of ATL and an alternative scheme with low doses of antimony is the motive for this study in Rio de Janeiro.
详细描述
- Introduction. Pentavalent antimonials are first line drugs for the treatment of leishmaniasis. WHO and Brazilian Ministry of Health recommend treating patients with cutaneous leishmaniasis (CL) with doses of 20mg/kg/day, IM or IV, for three to four weeks. In the Reference Centre on Leishmaniasis - IPEC - FIOCRUZ, the dose of 5mg/kg/day IM has been effective and well tolerated in the treatment of CL. CL is treated for 30 days, with a lower incidence of adverse effects and lower treatment dropout rates. In all cases patients should be monitored with clinical examination, electrocardiogram (EKG), blood count, liver, renal and pancreatic function tests. Some side effects can be observed, although they not necessarily lead to discontinuation of treatment. EKG most frequent abnormalities are heart rhythm and disturbances of ventricular repolarization: flattening or inversion of T wave and adjusted QT space widening.
- Background: Ideally, the most appropriate antimoniate therapeutic regimens should be established for each area, based on their efficacy and toxicity, without ignoring the difficulties of administration and cost. The treatment of CL must achieve healing of skin lesions and prevention of late mucosal involvement. The recognition, recommendation and acceptance of new regimens should be preceded by demonstration of their superiority to currently recommended treatments. We aim to compare the effectiveness and safety among treatment schemes with meglumine antimoniate currently recommended in Brazil for the treatment of CL and the alternative scheme with low dose of antimony.
- Objectives. 3.1. General Objective. To compare the effectiveness and safety of 20 days of 20 mg/kg/day meglumine antimoniate with 30 days of 5 mg/kg/day meglumine antimoniate in the treatment of patients with CL.
3.2. Specific Objectives. 3.2.1. To evaluate non-inferiority of low dose group as compared to the high dose antimonial therapy for CL.
3.2.2. To compare the effectiveness immediately and up to two years after treatment, of the different groups of antimonial therapy for CL.
3.2.3. To compare the frequency and severity of clinical, laboratory and EKG adverse events between different antimonial treatment groups.
3.2.4. To compare the frequency and severity of adverse events between elderly and young people between the groups.
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 (Care Provider)
入排标准
- 年龄范围
- 13 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
High dose
High dose: 20 days of 20 mg/kg/day meglumine antimoniate
干预措施: Meglumine antimoniate (Drug)
Low dose
Low dose: 30 days of 5 mg/kg/day meglumine antimoniate
干预措施: Meglumine antimoniate (Drug)
结局指标
主要结局
Effectiveness of meglumine antimoniate treatment
时间窗: 6 years
To compare the effectiveness of meglumine antimoniate at a dose of 5 mg or 20 mg Sb5+ / kg / day in the treatment of patients with cutaneous leishmaniasis.
次要结局
- Safety of meglumine antimoniate treatment(6 years)
研究者
ASchubach
Senior Researcher
Oswaldo Cruz Foundation