Combination Therapy in Indian Visceral Leishmaniasis

NCT00523965 | Completed Phase 3 DMC

• 1 other identifier: VLCombo 07
• Study Type: interventional
• Target: 624
• Locations: 1 country
• Sites: 1

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

Keywords

Kala-azar; miltefosine; liposomal amphotericin B

Outcome Measures

Primary Outcomes (2)

• Final cure at six month follow up

  18 months

• Cure at six month follow up

  12 months

Secondary Outcomes (1)

• Initial cure at the end of treatment

  12 months

Study Arms (4)

A

EXPERIMENTAL

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

Drug: Liposomal Amphotericin B with Miltefosine

B

EXPERIMENTAL

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

Drug: Liposomal Amphotericin B and Paromomycin Sulfate

C

EXPERIMENTAL

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

Drug: miltefosine + Paromomycin sulfate

D

ACTIVE COMPARATOR

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

Drug: amphotericin B deoxycholate

Interventions

amphotericin B deoxycholate DRUG

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

D

Liposomal Amphotericin B with Miltefosine 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

A

Liposomal Amphotericin B and Paromomycin Sulfate 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

B

miltefosine + Paromomycin sulfate 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

C

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients \> 5 years old with symptoms and signs of kala-azar (fever, weight loss, splenomegaly) and parasites demonstrated by microscopy in splenic aspirate smear

You may not qualify if:

• 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

Sponsors & Collaborators

• Banaras Hindu University: lead
• Drugs for Neglected Diseases: collaborator
• Rajendra Memorial Research Institute of Medical Sciences: collaborator

Study Sites (1)

Kala-azar Medical Research Center

Muzaffarpur, Bihar, 842001, India

Location

MeSH Terms

Conditions

Leishmaniasis, Visceral

Interventions

amphotericin B, deoxycholate drug combination; liposomal amphotericin B; miltefosine; Paromomycin

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Shyam Sundar, MD

  Institute of Medical Sciences, Banaras HIndu University

  PRINCIPAL INVESTIGATOR

• P K Sinha, MD

  Rajendra Memorial Research Insititute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: September 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: February 1, 2010
• Last Updated: May 26, 2010

Record last verified: 2009-01

Locations

IN (1)