Combination Therapy in Indian Visceral Leishmaniasis

This study has been completed.

Sponsor:

Collaborators:

Drugs for Neglected Diseases

Rajendra Memorial Research Institute of Medical Sciences

Information provided by:

Banaras Hindu University

ClinicalTrials.gov Identifier:

NCT00523965

First received: August 31, 2007

Last updated: May 25, 2010

Last verified: January 2009

History of Changes

Tracking Information

First Received Date ^ICMJE

August 31, 2007

Last Updated Date

May 25, 2010

Start Date ^ICMJE

September 2007

Primary Completion Date

August 2009 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Final cure at six month follow up [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Cure at six month follow up [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Original Primary Outcome Measures ^ICMJE

Final cure at six month follow up [ Time Frame: 18 months ]

Change History

Complete list of historical versions of study NCT00523965 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Initial cure at the end of treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Original Secondary Outcome Measures ^ICMJE

Initial cure at the end of treatment [ Time Frame: 12 months ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Combination Therapy in Indian Visceral Leishmaniasis

Official Title ^ICMJE

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)

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 Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

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

Condition ^ICMJE

Leishmaniasis, Visceral

Intervention ^ICMJE

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

Study Arm (s)

Experimental: 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

Intervention: Drug: Liposomal Amphotericin B with Miltefosine
Experimental: 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

Intervention: Drug: Liposomal Amphotericin B and Paromomycin Sulfate
Experimental: 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

Intervention: Drug: miltefosine + Paromomycin sulfate
Active Comparator: D
amphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions

Intervention: Drug: amphotericin B deoxycholate

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Estimated Enrollment ^ICMJE

624

Completion Date

February 2010

Primary Completion Date

August 2009 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

12 Years to 60 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

India

Administrative Information

NCT Number ^ICMJE

NCT00523965

Other Study ID Numbers ^ICMJE

VLCombo 07

Has Data Monitoring Committee

Yes

Responsible Party

Shyam Sundar, Drugs for Neglected Diseases Initiative

Study Sponsor ^ICMJE

Banaras Hindu University

Collaborators ^ICMJE

Drugs for Neglected Diseases
Rajendra Memorial Research Institute of Medical Sciences

Investigators ^ICMJE

Principal Investigator:	Shyam Sundar, MD	Institute of Medical Sciences, Banaras HIndu University
Principal Investigator:	P K Sinha, MD	Rajendra Memorial Research Insititute of Medical Sciences

Information Provided By

Banaras Hindu University

Verification Date

January 2009

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

To Top