Leishmaniasis, Visceral
Conditions
Keywords
Kala-azar, miltefosine, liposomal amphotericin B
Brief summary
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.
Interventions
Amphotericin B deoxycholate 1 mg/kg on alternate days for 15 infusions
DRUGLiposomal Amphotericin B with Miltefosine
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
DRUGLiposomal Amphotericin B and Paromomycin Sulfate
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
DRUGmiltefosine + Paromomycin sulfate
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
Sponsors
Drugs for Neglected Diseases
Rajendra Memorial Research Institute of Medical Sciences
Banaras Hindu University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Final cure at six month follow up | 18 months |
| Cure at six month follow up | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Initial cure at the end of treatment | 12 months |
Countries
India
Outcome results
None listed