Combination Therapy in Indian Visceral Leishmaniasis

Banaras Hindu University624 enrolled

Overview

Rationale The overall objective of this trial is to identify a safe and effective combination, (co-administration) short course treatment for the treatment of VL which could be easily deployed in a control programme. The hypothesis is that the combination treatment is as effective or better than the 5 mg/kg single dose of AmBisome and will reduce the risk of parasite resistance occurring. Safety and tolerability should be such that the combination can be easily deployed. Objective The specific primary and secondary objectives are as follows: Primary objective: To identify a short course combination treatment regimen which is at least as effective as a single dose of AmBisome 5mg/kg Secondary objective: To compare safety and tolerability of the various treatments measured by vital signs, blood biochemistry, (renal and liver function tests) haematology, spontaneous and elicited adverse event reporting Primary Endpoint: The primary efficacy endpoint variable is parasitological clearance 2 weeks after start of treatment with no relapse during follow up and no clinical signs or symptoms of VL at 6 months post treatment. Parasitology is only carried out at any time during follow-up or at six months post treatment if there are signs or symptoms of VL infection.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

624

Conditions

Leishmaniasis, Visceral

amphotericin B deoxycholateDRUG

Amphotericin B deoxycholate 1 mg/kg on alternate days for 15 infusions

Liposomal Amphotericin B with MiltefosineDRUG

Liposomal Amphotericin B 5 mg Miltefosine 50 mg twice daily if patient weighs equal to or \> 25 kg Miltefosine 50 mg once daily if patient weighs \<25 mg

Liposomal Amphotericin B and Paromomycin SulfateDRUG

AmBisome 5mg/kg iv infusion over 2 h x 1 day (single dose) + paromomycin sulfate 15 mg/kg/day i.m for 10 days, on day 2-11

miltefosine + Paromomycin sulfateDRUG

oral miltefosine 50mg once daily (\< 25 kg body weight) or twice daily ( \> 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 10 days + Paromomycin sulfate 15 mg/kg/day im. for 10 days

Eligibility

Sex: ALLMin age: 12 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients \> 5 years old with symptoms and signs of kala-azar (fever, weight loss, splenomegaly) and parasites demonstrated by microscopy in splenic aspirate smear Exclusion Criteria: * Pregnant or breast-feeding women * Individuals seropositive to HIV or individuals with a serious concurrent infection such as tuberculosis or bacterial pneumonia. * Women of child-bearing age will be counseled about adequate birth control during and for three months after miltefosine treatment and provided with a satisfactory method of contra-ception. * Granulocyte count \< 1,000/mm3, hemoglobin \< 5 g/dL or platelet count \< 40,000/mm3 * Hepatic transaminases or total bilirubin greater than three times normal * Serum creatinine \> 2.0 mg/dL * Prothrombin time \> 5 seconds above control * Inability of subject or guardian to provide written informed consent

Outcomes

Primary Outcomes

Final cure at six month follow up

Time frame: 18 months

Cure at six month follow up

Time frame: 12 months

Secondary Outcomes

Initial cure at the end of treatment