Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar

Study Overview
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Brief Summary
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Miltefosine and liposomal amphotericin B (AmBisome) are approved drugs for visceral leishmaniasis. In this study both drugs will be given in a sequential manner. AmBisome will be given on day 1, followed by Miltefosine for 14 days. Final Cure will be evaluated at six months.

Detailed Description
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Methodology Multicenter trial, eligible patients will be treated with Liposomal amphotericin B (5 mg/kg) on day 1 and then with miltefosine capsules for 14 days (days 2-15). At two weeks after the end of treatment the initial cure (clinical and parasitological cure) and the clinical response will be determined. If initial cure is observed, a patient will be evaluated after a 6 months (after end of treatment) follow up period for final clinical cure. Number of patients planned Total number of patients planned: 150 patients at both centers combined. 75 pediatric (2-11 years); 75 adult (12-65 years). Lack of suitability for the trial: Post Kala-azar Dermal Leishmaniasis (PKDL) Concomitant treatment with other anti-leishmanial drugs Any condition which compromises ability to comply with the study procedures Administrative reasons: Any condition or situation that compromises compliance with study procedures including follow-up visit Study medication, dose and mode of administration Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15) Dosage: weighing ≥ 25 kg: 100 mg miltefosine daily as one capsule (50 mg) in the morning and one capsule in the evening, after meals for 14 days. weighing < 25 kg: 50 mg miltefosine daily as one capsule (50 mg) in the morning, after meals for 14 days. Parameter for evaluation Final cure rate (initial parasite cure and clinical assessment at six month EOT) Initial parasitological cure rate (based on splenic aspirates or Bone marrow aspirate) Clinical response at end of treatment (clinical assessment) Adverse events Statistical methods Calculation of cure rate with 95% and 90% lower confidence limit according to Clopper Pearson Calculation of overall incidence of adverse events

Official Title
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The Efficacy and Safety of a Short Course of Miltefosine and Liposomal Amphotericin B for Visceral Leishmaniasis in India

Conditions
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Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Liposomal amphotericin B and Miltefosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female age between 2 and 65 years (inclusive) Parasites visualized on splenic aspiration Signs and symptoms compatible with visceral leishmaniasis (e.g. fever, splenomegaly, anaemia, weight loss, leucopenia, thrombocytopenia) Confirmed diagnosis of VL by visualization of parasites on splenic/bone marrow aspirate Fever for at least 2 weeks Written informed consent from the patient/or from parent or guardian if under 18 years old Exclusion Criteria: Hemoglobin < 6 g/dl White blood cell count < 1000/mm3 Platelets <50,000 Prothrombin time > 5 sec above control ASAT > 3 times the upper limit of normal Serum creatinine or BUN > 1.5 times the upper limit of normal Malaria Tuberculosis HIV positive serology Lactation, pregnancy Refusing contraception method during treatment period plus 3 months Any medical condition(s) that upon judgment of physician may affect the safety of the patient when treated with study drugs Any concomitant drug that is nephrotoxic

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15) | Drug: Liposomal amphotericin B and Miltefosine<br>* Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)<br>* Other names: AmBisome and Impavido;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final Cure six months after the end of treatment |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Visceral leishmaniasis, kala-azar, miltefosine, AmBisome