Secondary Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients Using Pentamidine as a Prophylactic Agent: a Prospective Cohort Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 3
- 主要终点
- Number of Participants With Serious Adverse Events (SAEs)
研究概览
简要总结
Visceral leishmaniosis (VL) is widely reported in Ethiopia, with about 30% of cases being associated with human immunodeficiency virus (HIV). In absence of antiretroviral treatment (ART), poor prognosis, high mortality and high relapse rates are characteristic of Ethiopian VL patients with HIV co-infection. Conversely, co-infection can be successfully managed via a combination of effective treatment of the initial episode, timely ART and prevention of relapses.
Actually, until cellular immunity returns with ART, the patient is at risk of VL relapses, which can result in death, severe illness, reduced ART efficacy, drug-resistance and possibly transmission of drug-resistant Leishmania donovani. Patients most vulnerable to relapses are those with high levels of immunosuppression, with previous VL episodes, or with opportunistic infections (OIs). The most important factor to prevent relapses seems to be the clearance of visible parasites.
Limited studies in Europe show that HIV co-infected patients may benefit from secondary prevention with antimonials (part of mainstay treatment for VL in Ethiopia) and pentamidine (PM), not used for VL treatment in Africa. Such maintenance treatment has not been studied in African VL, but the poor outcomes without secondary prevention highlight a need of better care to patients at risk of relapse.
This prospective cohort study aims at documenting the patient's outcomes of secondary prophylaxis with PM in VL-HIV co-infection, in terms of time to relapse or death, safety and feasibility, before it can be considered for general use in Ethiopia. A placebo group is not included, due to the clear advantages of the intervention to the patient population.
详细描述
Visceral leishmaniosis (VL) in Ethiopia has been reported in different parts of the country, with approximately 30% of cases being associated with human immunodeficiency virus (HIV). The ruralisation of HIV epidemic in VL endemic areas will hamper efforts to control VL. Clinical experience in Ethiopia has shown that anti-leishmanial treatment in the absence of anti-retroviral therapy (ART) does not result in favourable outcomes: poor prognosis, high mortality and relapse rates are characteristic of Ethiopian VL patients with HIV co-infection. The effective management of the initial VL episode, timely ART, and prevention of relapses should be the cornerstones of effective management of HIV/VL co-infection.
However, parasitological cure of VL in HIV co-infected patients cannot easily be established, and until cellular immunity returns with ART, the patient is at risk of relapses of VL, which can result in death, severe illness, negative effect on ART efficacy leading to other opportunistic infections (OIs), emergence of drug-resistant parasites, and possibly to transmission of drug-resistant Leishmania donovani. Patients most vulnerable to relapses are 1) those with high levels of immunosuppression, 2) patients with previous VL episodes, and 3) patients with OIs.
ART reduces the risk of VL relapse/recurrence by ~50%, while the type of anti-leishmanial primary treatment has little effect on relapses; the most important factor seems to be clearance of visible parasites (if residual parasites are seen at the end of treatment, the relapse rate is 100%).
Limited studies in Europe show that HIV co-infected patients may benefit from secondary prevention, by significantly prolonging the relapse-free period. The drugs studied for secondary prophylaxis in Europe have been meglumine antimoniate and AmBisome, which are part of mainstay treatment for VL in Ethiopia, and pentamidine (PM), which is not used for VL treatment in Africa. The effect of such maintenance treatment has not been studied in African VL, but the poor outcomes without secondary prevention highlight a clear need to offer better care to patients at high risk of relapse.
Indeed, secondary prophylaxis is generally recommended in Europe and the United States (see the 2009 Center for Disease Control guidelines). PM 4 mg/kg intravenous (IV) every 3-4 weeks has been proposed as secondary prophylaxis, and it is already used in countries like United Kingdom and Spain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with Visceral Leishmaniosis (VL) during the recruitment period that are EITHER treated for VL relapse and have a documented negative test of cure (TOC), OR are treated for primary VL and have a documented CD4 <200 or WHO stage 4 disease during the recruitment period and have a documented negative TOC
- •Patients treated for VL in the past with documented CD4 <200 or WHO stage 4 disease during the recruitment period AND documented negative TOC after the latest VL treatment and currently asymptomatic OR currently negative diagnostic test (microscopy)
- •Patients agreeing to start or continue antiretroviral treatment (first or second line)
- •Patients willing to provide written informed consent
排除标准
- •Patients with known hypersensitivity to pentamidine
- •Patients with known renal failure
- •Patients with diabetes mellitus (type I or II)
- •Patients unlikely to attend follow-up visits/comply with study requirements
- •Pregnant and lactating women
- •Any other condition that could increase the risk of toxicity of pentamidine to such an extent outweighing the expected benefit (eg severe cardiac dysfunction).
研究组 & 干预措施
Pentamidine Secondary Prophylaxis (PSP)
Patients with co-infection of human immunodeficiency virus (HIV)and visceral leishmaniosis (VL), having being treated for VL, are allocated to pentamidine secondary prophylaxis, to prevent VL relapses. The treatment period is of 12 months, plus an "extended treatment period" of 0 to 6 months depending on the immunosuppression status, plus 12 months follow-up after the extended treatment period.
干预措施: Pentamidine (Drug)
结局指标
主要结局
Number of Participants With Serious Adverse Events (SAEs)
时间窗: 1 year
Number of patients with SAEs which are possibly, probably or definitely drug-related following clinician's assessment or that lead to permanent drug discontinuations during the first year of pentamidine administration
Probability of Relapse-free Survival
时间窗: up to 1 year after the start of the intervention (PSP)
Probability of relapse-free survival up to one year after the start of the intervention (PSP) (at month 6 and month 12)
次要结局
- Number of Required Additional Interventions(30 months)
- Number of Participants With Adverse Events(1 year)
- Number of Treatment Discontinuations and Interruptions(30 months)