Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar
Condition: Visceral Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Visceral
Study type: Interventional
Phase: Phase 2

Summary: 
      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: 
      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:

        1. 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.

        2. 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
    

Intervention name(s): Liposomal amphotericin B and Miltefosine
Intervention type(s): Drug
Intervention description(s): 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)
Other intervention name(s): AmBisome and Impavido
Intervention MeSH terms: Amphotericin B; Liposomal amphotericin B; Miltefosine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Visceral leishmaniasis; kala-azar; miltefosine; AmBisome