A randomized trial of AmBisome® monotherapy and combination of AmBisome® and miltefosine for the treatment of Visceral Leishmanaisis in HIV positive patients in India
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- The primary endpoint is cure at day 210 and is defined as survival and being symptom free of VL at day 210.
研究概览
简要总结
One third ofall HIV patients worldwide live in regions where leishmaniasis is endemic [1]. Visceral leishmaniasis (VL) caused by the parasite L.donovani is endemic to Bihar, a populous state of 110 million people in East India, which carries an estimated 40% of the world’s VL burden [2]. Although Bihar has a relatively low prevalence of HIV (between 0.22 - 0.33%), its high population density means that in absolute numbers an estimated 300,000 people in the state live with HIV/AIDS [3].
The evidence base regarding best treatment practices for co-infected patients worldwide is limited, due to a lack of randomized trials and to the fact that most available data comes from observational studies with relatively short follow-up periods, and often with high rates of loss to follow-up [15]. Nevertheless, worse outcomes in almost every respect have consistently been reported in this patient group when compared to patients not known to be HIV-positive—for example, in terms of higher relapse rates, mortality, and VL drug toxicity and treatment failure [15].
Considering the lack of quality evidence surrounding treatment for co-infected patients in the Indian context, we suggest that a study examining the effectiveness of 40mg/kg AmBisome® — as recommended by the WHO for VL-HIV co-infection [17] but never tested in India or on L. donovaniin the Indian subcontinent— and a lower dose combination of AmBisome® and miltefosine be formally evaluated in order to provide the Indian policy makers with evidence to develop specific guidelines for the treatment of co-infected patients. Note that this evidence gap is also being currently addressed in Ethiopia, where a clinical trial in co-infected patients comparing two arms (AmBisome monotherapy and AmBisome – miltefosine combination therapy) is currently underway [31]. However, the very different behavior of the parasite between the two regions means that results cannot be extrapolated from one region to another.
This protocol will evaluate the efficacy and safety of the combination of AmBisome® 30 mg/kg with miltefosine (100 mg daily for 14 days) and AmBisome® monotherapy (high dose: 40 mg/kg) in Bihar, India.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: Confirmed HIV positive test (2 rapid diagnostics tests (RDTs) as per National Programme guidelines, WB for any discrepancy Diagnosis of VL confirmed by bone marrow or spleen aspirate.
- •Male and female age ≥ 18 years Written informed consent from the patient.
排除标准
- •Women of child-bearing potential 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.
- •Pregnant women or breast-feeding mothers.
- •Clinical or biological evidence of severe cardiac, renal or hepatic impairment.
- •Known hypersensitivity to AmBisome® and/or miltefosine.
- •Concomitant severe infection such as TB or other serious underlying disease that would preclude evaluation of patients response to study medication Hb <5mg/dl, WBC <1x103/mm3, platelets <40,000/mm3 Abnormal liver function tests (ALT/AST) more than 3 times the upper limit of normal Creatinine >1.2.
结局指标
主要结局
The primary endpoint is cure at day 210 and is defined as survival and being symptom free of VL at day 210.
时间窗: Day 210
次要结局
- Relapse-free survival of patients with no concurrent TB infection at 6 and 12 months defined as:(The patient has no diagnosis of TB prior to day 58 and is alive and disease-free (defined as absence of signs and symptoms of VL or if symptomatic, a negative parasitological assessment by tissue aspirate) at day 210 and remains disease free and alive from day 210 (if initially cured) until the last follow up assessment (i.e. day 390).)
- Safety(Assessment of safety during treatment and follow-up based on clinical adverse events, laboratory parameters during treatment and 1 month follow up.)
- Relapse-free survival at 12 months as defined as:(- The patient being alive and symptom-free from day 210 (if initially cured) and remains symptom-free until the last follow up assessment (i.e. day 390).)
- Initial cure at Day 29 as defined as:(Patient presents clinical improvement, defined as cessation of fever and reduction in any initial splenomegaly and a negative parasitological assessment by tissue aspirate.)