A Randomised, Open-label, Parallel-group, Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens (Co-administration), of AmBisome, Paromomycin and Miltefosine in Visceral Leishmaniasis (VL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 624
- 试验地点
- 1
- 主要终点
- Final cure at six month follow up
研究概览
简要总结
Rationale
The overall objective of this trial is to identify a safe and effective combination, (co-administration) short course treatment for the treatment of VL which could be easily deployed in a control programme. The hypothesis is that the combination treatment is as effective or better than the 5 mg/kg single dose of AmBisome and will reduce the risk of parasite resistance occurring. Safety and tolerability should be such that the combination can be easily deployed.
Objective
The specific primary and secondary objectives are as follows:
Primary objective:
To identify a short course combination treatment regimen which is at least as effective as a single dose of AmBisome 5mg/kg
Secondary objective:
To compare safety and tolerability of the various treatments measured by vital signs, blood biochemistry, (renal and liver function tests) haematology, spontaneous and elicited adverse event reporting
Primary Endpoint:
The primary efficacy endpoint variable is parasitological clearance 2 weeks after start of treatment with no relapse during follow up and no clinical signs or symptoms of VL at 6 months post treatment.
Parasitology is only carried out at any time during follow-up or at six months post treatment if there are signs or symptoms of VL infection.
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
- 12 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients > 5 years old with symptoms and signs of kala-azar (fever, weight loss, splenomegaly) and parasites demonstrated by microscopy in splenic aspirate smear
排除标准
- •Pregnant or breast-feeding women
- •Individuals seropositive to HIV or individuals with a serious concurrent infection such as tuberculosis or bacterial pneumonia.
- •Women of child-bearing age will be counseled about adequate birth control during and for three months after miltefosine treatment and provided with a satisfactory method of contra-ception.
- •Granulocyte count < 1,000/mm3, hemoglobin < 5 g/dL or platelet count < 40,000/mm3
- •Hepatic transaminases or total bilirubin greater than three times normal
- •Serum creatinine > 2.0 mg/dL
- •Prothrombin time > 5 seconds above control
- •Inability of subject or guardian to provide written informed consent
研究组 & 干预措施
A
AmBisome 5 mg/kg iv infusion over 2 h x 1 day (single dose) + oral miltefosine 50mg once daily (< 25 kg body weight) or twice daily ( > 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 7 days on day 2-8
干预措施: Liposomal Amphotericin B with Miltefosine (Drug)
B
AmBisome 5mg/kg iv infusion over 2 h x 1 day (single dose) + paromomycin sulfate 15 mg/kg/day i.m for 10 days, on day 2-11
干预措施: Liposomal Amphotericin B and Paromomycin Sulfate (Drug)
C
oral miltefosine 50mg once daily (< 25 kg body weight) or twice daily ( > 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 10 days + Paromomycin sulfate 15 mg/kg/day im. for 10 days
干预措施: miltefosine + Paromomycin sulfate (Drug)
D
amphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions
干预措施: amphotericin B deoxycholate (Drug)
结局指标
主要结局
Final cure at six month follow up
时间窗: 18 months
Cure at six month follow up
时间窗: 12 months
次要结局
- Initial cure at the end of treatment(12 months)