Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 378
- 试验地点
- 5
- 主要终点
- Cure rate
研究概览
简要总结
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.
详细描述
Visceral leishmaniasis is a relevant public health problem in Brazil with approximately 3500 cases registered every year. Eight percent lethality rate has been observed during the past decade in spite of free of charge availability of antileishmanial drugs supplied by the public health system.
The present study was designed as a phase IV, multicentric, open label, active controlled clinical trial targeted to visceral leishmaniasis adult and pediatric cases.
The current drugs approved for visceral leishmaniasis treatment in Brazil will be compared in four treatment groups: meglumine antimoniate, amphotericin B deoxycholate, liposomal amphotericin B and a combination of single dose of liposomal amphotericin B plus meglumine antimoniate. Meglumine antimoniate treated patients will constitute the active control group.
Drugs will be compared based on the cure rate observed after six months follow-up.
The study arm submitted to treatment with Amphotericin B deoxycholate was suspended in September 2012.
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
- None
入排标准
- 年龄范围
- 6 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients with visceral leishmaniasis characterized by fever plus hepatomegaly or splenomegaly with at least one positive result in the following laboratory tests:
- •direct observation of leishmania amastigotes in bone marrow smear
- •leishmania in vitro culture from bone marrow aspirates
- •leishmania kDNA amplification by PCR in bone marrow or peripheral blood samples
- •rK39 immunochromatographic rapid test performed on serum sample
排除标准
- •pregnancy
- •HIV infection
- •chronic diseases such as diabetes mellitus,kidney, liver or cardiac diseases, schistosomiasis, malaria or tuberculosis
- •immune disorders or use of drugs which interferes with the immune response
- •treatment with drugs with increased risk for toxicity associated with the study drugs
- •exposure to antileishmanial drugs during the past six months
- •I.V. drug users
- •episodes of visceral leishmaniasis relapse
- •hypersensibility to the study drugs
- •difficulties for accomplishing the follow-up schedule
- •any of the following clinical signs of laboratory abnormalities: hepatic encephalopathy, generalized edema, toxemic individuals, severe malnutrition, jaundice, abnormal serum creatinine, bilirubin, INR > 2,0, platelet count < 20000/mm3
研究组 & 干预措施
Meglumine antimoniate
Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.
干预措施: Antimoniate of N-methylglucamine (Drug)
Liposomal Amphotericin B
Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.
干预措施: Liposomal amphotericin B (Drug)
Amphotericin B
Amphotericin B deoxycholate 1mg/kg/d I.V. for 14 consecutive days. This arm was suspended in September 19th, 2012, because of a relevant excess of adverse events and serious adverse events associated with this experimental intervention in comparison with the active comparator and the other two experimental arms. The suspension of this study arm was supported by a DSMB statement.
干预措施: amphotericin B deoxycholate (Drug)
Combination therapy
Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10.
干预措施: Liposomal amphotericin B (Drug)
Combination therapy
Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10.
干预措施: Antimoniate of N-methylglucamine (Drug)
结局指标
主要结局
Cure rate
时间窗: 6 month
Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up.
次要结局
- Relapse rate((6 months post treatment) After treatment until the sixth month of follow-up)
- Improvement rate(30 days)
- Serious adverse events rate(During (day one) and within the six months follow-up)
- Adverse event rate and intensity(During (day one) treatment and within the six months follow-up)
研究者
Gustavo Adolfo Sierra Romero
Professor
University of Brasilia