Combination Therapy in Indian Visceral Leishmaniasis

NCT ID: NCT00523965

Last Updated: 2010-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 624 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-02-28

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.

Conditions

Leishmaniasis, Visceral

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

AmBisome 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

Group Type: EXPERIMENTAL

Liposomal Amphotericin B with Miltefosine

Intervention Type: DRUG

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

B

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

Group Type: EXPERIMENTAL

Liposomal Amphotericin B and Paromomycin Sulfate

Intervention Type: DRUG

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

C

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

Group Type: EXPERIMENTAL

miltefosine + Paromomycin sulfate

Intervention Type: DRUG

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

D

amphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions

Group Type: ACTIVE_COMPARATOR

amphotericin B deoxycholate

Intervention Type: DRUG

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

Interventions

amphotericin B deoxycholate

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Drugs for Neglected Diseases

OTHER

Sponsor Role: collaborator

Rajendra Memorial Research Institute of Medical Sciences

OTHER

Sponsor Role: collaborator

Banaras Hindu University

OTHER

Sponsor Role: lead

Responsible Party

Drugs for Neglected Diseases Initiative

Principal Investigators

Shyam Sundar, MD

Role: PRINCIPAL_INVESTIGATOR

Institute of Medical Sciences, Banaras HIndu University

P K Sinha, MD

Role: PRINCIPAL_INVESTIGATOR

Rajendra Memorial Research Insititute of Medical Sciences

Locations

Kala-azar Medical Research Center

Muzaffarpur, Bihar, India

Countries

India

Other Identifiers

VLCombo 07

Identifier Type: -

Identifier Source: org_study_id