A Phase III, Open Label, Randomised, Study of Three Short Course Combination Regimens (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome® Alone for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 602
- 试验地点
- 4
- 主要终点
- Definitive cure
研究概览
简要总结
This protocol will evaluate the efficacy and safety of various combinations of the three drugs; AmBisome, Paromomycin and Miltefosine at reduced total dosage against the standard treatment with a total dose of 15mg/kg of AmBisome.
详细描述
Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. The causative parasite in Bangladesh is almost exclusively L. donovani.
• The current treatment options in Bangladesh are not satisfactory as they are either toxic and long, or are of limited use in women of childbearing age due to possible teratogenicity, long treatment duration which leads to non-compliance and possible emergence of resistance or expensive.
In collaboration with Indian Medical Research Council and investigators in India, DNDi initiated a combination trial for treatment of VL in Bihar, India in 2008 including 624 patients from age 5 - 60. The same combinations will be used in the present study. An interim safety review was conducted on the first 120 patients included in the Indian VL Combination study and revealed no safety issues with combination treatment. The enrolment is complete and the final results for 624 patients are expected in Q1 2010.
This is a randomized, controlled, open-label, parallel group study to compare the safety and efficacy of different combination regimens with AmBisome for the treatment of VL in Bangladesh.
This trial is designed in two steps:
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
- 5 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •VL proven by parasitological examination of splenic or bone marrow aspirate. Parasite burden to be graded according to Chulay and Bryceson 1983 and subsequently adopted by WHO. (Step 1 only)
- •History of fever, for at least 2 weeks with one or more of the followings criteria: Anaemia (5<Hb<10g/dl), Loss of weight, Splenomegaly
- •rk39 positive at baseline assessments
- •willing and able to attend follow-up visits
- •Male or Female age: 5-60 yrs
- •Written informed consent from the patient or from patient's parent or guardian if the patient is under 18 yrs, in addition written assent from patients of 11 - 17 yrs of age. If the patient or parent/guardian are illiterate an impartial witness should be present during the consenting procedure and should also sign.
排除标准
- •Married women of child-bearing potential (defined as women who have achieved menarche) who are not using an assured method of contraception or are unwilling to use an assured method of contraception for the duration of treatment and three months after. Assured methods of contraception include i.e. IUCD or depot hormone injection of medroxyprogesterone acetate MPA (DepoProvera®)
- •Platelet count less than 40,000/mm3 (Step 1 only)
- •Prothrombin time 5 seconds or greater than normal range (Step 1 only)
- •Known hepatitis B, C or known HIV positive
- •Patients who present with Para Kala-azar Dermal Leishmaniasis
- •Signs/symptoms indicative of severe VL (Hb < 5gm/dl, etc)
- •Patients with a previous history of VL
- •Patients who have received any investigational (unlicensed) drugs within the last 3 months
- •Severe malnutrition BMI<15 in adults, weight for height less than 60% in children
- •Clinical symptoms of chronic underlying disease such as severe cardiac, renal or hepatic impairment
- •Positive HRP2/pLDH Combo test for malaria
- •Pregnant woman or breast-feeding mother
- •Known alcohol or other drug abuse
- •Concomitant chronic drug treatment eg. TB, HIV etc.
- •Known hypersensitivity to AmBisome, Paromomycin and other aminoglycosides and/or Miltefosine
研究组 & 干预措施
Ambisome
15mg Ambisome on days 1,3 and 5
干预措施: Liposomal amphotericin B (Drug)
Ambisome + Miltefosine
Ambisome 5mg + miltefosine 10 days
干预措施: liposomal amphotericin B + miltefosine (Drug)
Ambisome +paromomycin
AmBisome IV infusion (single dose, day 1) + Paromomycin base 11mg/kg/day IM (Gland Pharma, India) for 10 days (days 2-11)
干预措施: liposomal amphotericin B + paromomycin (Drug)
Miltefosine + paromomycin
Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10) + Paromomycin base 11mg/kg/day IM for 10 days (days 1-10).
干预措施: Miltefosine + Paromomycin (Drug)
结局指标
主要结局
Definitive cure
时间窗: 6 month post treatment
The primary endpoint variable is definitive cure at month 6, and is defined as no significant clinical signs or symptoms of VL at Day 45 including lack of fever \[axiliary temperature \< 99.5°F\] and at least one of the following: * improved Hb if the patient was anaemic at baseline (Hb\< 8g/dl) * spleen regression if the spleen was palpable on admission and absence of clinical signs and symptoms of VL (fever, weight loss, splenomegaly) at any time during 6 months post treatment period.
次要结局
- Initial Cure(Day 45)
- Adverse events(Treatment)