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Combination Therapy in Indian Visceral Leishmaniasis

Phase 3
Completed
Conditions
Leishmaniasis, Visceral
Interventions
Drug: Liposomal Amphotericin B with Miltefosine
Drug: Liposomal Amphotericin B and Paromomycin Sulfate
Registration Number
NCT00523965
Lead Sponsor
Banaras Hindu University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
624
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cmiltefosine + Paromomycin sulfateoral 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
Damphotericin B deoxycholateamphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions
ALiposomal Amphotericin B with MiltefosineAmBisome 5 mg/kg iv infusion over 2 h x 1 day (single dose) + 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 7 days on day 2-8
BLiposomal Amphotericin B and Paromomycin SulfateAmBisome 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
Primary Outcome Measures
NameTimeMethod
Final cure at six month follow up18 months
Cure at six month follow up12 months
Secondary Outcome Measures
NameTimeMethod
Initial cure at the end of treatment12 months

Trial Locations

Locations (1)

Kala-azar Medical Research Center

🇮🇳

Muzaffarpur, Bihar, India

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