A Pilot Project To Evaluate The Safety And Effectiveness Of New Treatment Modalities For The Management Of Visceral Leishmaniasis (VL) In The Endemic Regions Of India
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 7,000
- 试验地点
- 13
- 主要终点
- The effectiveness or final proportion cured (success) of the treatments proposed will reach a target of 95%. Therefore the proportion of observed failures will be 5% for each of the proposed treatments.
研究概览
简要总结
This is an open-label, prospective, non randomised, non comparative, multicenter, observational pharmacovigilence study of the safety and effectiveness of new treatment modalities to treat VL in public sector of India.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
The objectives stated above will be achieved through:
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The implementation of a PV network to evaluate safety across all the participating VL treatment sites. This will also involve the development of a reporting system for individual Serious and unexpected ADRs to a steering committee and the relevant authorities.
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The development of a VL treatment and follow up surveillance register (referred to hence as the ‘surveillance register’) listing all patients that receive one of the new treatment modalities in the participating sites and the periodic reporting of aggregated outcome data to the national authorities.
Sites:
In order to reflect the current situation of health care provision for VL in endemic areas, the project will be implemented in the following structures:
- Ministry of health structures from PHC level upwards: most centres and patients to be included in this project will be in this category.
- A few key health providers with experience managing VL (e.g. RMRIMS).
- In 5 PHCs and 1 district hospital in Vaishalli District, Bihar State, where Médecins Sans Frontières-Spain/OCBA is currently working within the government structures.
Treatments to be implemented (new treatment modalities)i) NON AmBisome® Based treatment: targeted for first line administration at the primary health care (PHC) level in a district
***Treatment 1:***MF&PM combination treatment given as follows:
· Miltefosine given orally for 10 days (day 1-10) at 100mg daily for adults over 25kg , 50mg daily for adults under 25kg, and 2.5mg/kg daily for children plus paromomycin 11mg/kg base given intramuscularly for 10 days (day 1-10): this treatment will be used in at least 5 PHCs.
ii) AmBisome® Based treatment: targeted for administration where AmBisome® is feasible in a district (i.e. PHCs able to maintain cold chain, familiar with amphotericin B administration, or district hospitals). AmBisome® based treatment modalities that will be evaluated consist of the following:
Treatment 2:
· AmBisome® 5mg/kg on day 1 plus miltefosine given orally at 100mg daily for adults over 25kg , 50mg daily for adults under 25kg, and 2.5mg/kg daily for children for 7 days (days 2-8): this treatment will be used in at least 5PHCs.
Treatment 3:
Single dose AmBisome® 10mg/kg on day 1: this treatment will be used at hospital and referral level in the district(s) involved.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 2.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Primary cases: all ‘new cases’ with clinical features of VL (fever for 2 weeks and splenomegaly) and are rk39 or parasitology positive.
- •Relapse cases: all cases that have previously been treated for VL (but not involving any one of the drugs that are part of the new treatment modality used at that treatment centre), have fever, splenomegaly and are confirmed by parasitology.
- •Written consent to receive one of the new treatment modalities and allow information to be collected as part of a pilot project.
排除标准
- •Pregnant women and women of child bearing age who cannot be assured contraceptive cover will be excluded from all miltefosine containing regimens.
- •These cases may be referred and managed with non-miltefosine new treatment modalities in the nearest district hospital/ designated referral centre.
- •Their exclusion will be recorded within the surveillance register.
- •All patients who have previously been treated with one of the drugs that are part of the new treatment modality in use at that centre will be excluded (e.g. any patient treated with miltefosine monotherapy will not be retreated with a miltefosine combination treatment; any patient treated with high dose AmBisome® will not be given single dose AmBisome® or an AmBisome® combination).
- •Their admission will however be recorded within the surveillance register.
- •All known HIV+ patients (see special cases below) patients will be treated with alternative regimens.
- •All PKDL patients will be treated with alternative regimens.
- •All patients with a history of allergy or hypersensitivity to the relevant drug Special cases A category of special cases will be defined on entry based on the classifications below.
- •These cases will either be managed by specific treatments (e.g. one particular new treatment modality) and/ or in specialist referral centres.
- •All pregnant women can be included and will be treated with AmBisome® 10mg/kg single dose.
- •All pregnant cases treated, or patients given a new treatment modality and who become pregnant within one month of end of treatment will be entered into a special pregnancy follow up register.
- •All women of child bearing age who cannot be assured contraceptive cover will be treated with either AmBisome® & paromomycin or AmBisome® single dose.
- •All patients with signs and symptoms of severe diseases: defined as severe anaemia (i.e. haemoglobin 4 and/ or signs of cardiac failure), renal failure or hepatic failure (e.g. jaundice), serious concomitant infection (e.g. severe pneumonia), severe malnutrition, will be referred to the nearest district hospital or RMRIMS for further specialist management.
- •These patients may be treated with one of the new treatment modalities according to the physician’s decision.
- •All patients with proven TB/VL co-infection will be referred to the nearest district hospital or RMRIMS for further specialist management.
- •All children under 2 will be referred to the nearest district hospital or RMRIMS for further specialist management.
- •However, as defined in the exclusion criteria, these patients will not be treated with one of the new treatment modalities.
- •Compassionate high dose therapy with AmBisome® or a high dose combination of drugs may be used according to the physician’s decision.
- •All consenting patients entering a centre where one of the new treatment modalities is being piloted will be entered in to a register.
结局指标
主要结局
The effectiveness or final proportion cured (success) of the treatments proposed will reach a target of 95%. Therefore the proportion of observed failures will be 5% for each of the proposed treatments.
时间窗: Initial Cure is 10 days and the final cure is 06 months
The level of expedited safety events reported (Deaths, Serious and Unexpected Adverse Drug reactions) will be ≤ 2% for each of the proposed treatments.
时间窗: Initial Cure is 10 days and the final cure is 06 months
次要结局
- Initial outcome: Initial cured, died, defaulted, treatment stopped, treatment failure, referred to another centre(Initial Cure is 10 days)