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

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

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