Combination Therapy in Indian Visceral Leishmaniasis

Leishmaniasis, Visceral Clinical Trial

Official title:

A Randomised, Open-label, Parallel-group, Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens (Co-administration), of AmBisome, Paromomycin and Miltefosine in Visceral Leishmaniasis (VL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523965
• Other study ID #: VLCombo 07
• Status: Completed
• Phase: Phase 3
• First received: August 31, 2007
• Last updated: May 25, 2010
• Start date: September 2007
• Est. completion date: February 2010

Study information

• Verified date: January 2009
• Source: Banaras Hindu University
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 624
• Est. completion date: February 2010
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral

Intervention

Drug:
• amphotericin B deoxycholate
Amphotericin B deoxycholate 1 mg/kg on alternate days for 15 infusions
• Liposomal 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
• Liposomal 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
• miltefosine + 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

Locations

Country	Name	City	State
India	Kala-azar Medical Research Center	Muzaffarpur	Bihar

Sponsors (3)

Lead Sponsor	Collaborator
Banaras Hindu University	Drugs for Neglected Diseases, Rajendra Memorial Research Institute of Medical Sciences

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final cure at six month follow up		18 months	Yes
Primary	Cure at six month follow up		12 months	No
Secondary	Initial cure at the end of treatment		12 months	Yes