Combination Therapy in Indian Visceral Leishmaniasis - Full Text View

Sponsor:	Banaras Hindu University
Collaborators:	Drugs for Neglected Diseases Rajendra Memorial Research Institute of Medical Sciences
Information provided by:	Banaras Hindu University
ClinicalTrials.gov Identifier:	NCT00523965

Purpose

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.

Condition	Intervention	Phase
Leishmaniasis, Visceral	Drug: amphotericin B deoxycholate Drug: Liposomal Amphotericin B with Miltefosine Drug: Liposomal Amphotericin B and Paromomycin Sulfate Drug: miltefosine + Paromomycin sulfate	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Leishmaniasis

Drug Information available for: Miltefosine Paromomycin sulfate Amphotericin B Paromomycin

U.S. FDA Resources

Further study details as provided by Banaras Hindu University:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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

Estimated Enrollment:	624
Study Start Date:	September 2007
Study Completion Date:	February 2010
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	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
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	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
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	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
Active Comparator: D amphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions	Drug: amphotericin B deoxycholate Amphotericin B deoxycholate 1 mg/kg on alternate days for 15 infusions

Eligibility

Ages Eligible for Study:	12 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523965

Locations

India
Kala-azar Medical Research Center
Muzaffarpur, Bihar, India, 842001

Sponsors and Collaborators

Banaras Hindu University

Drugs for Neglected Diseases

Rajendra Memorial Research Institute of Medical Sciences

Investigators

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

More Information

No publications provided

Responsible Party:	Shyam Sundar, Drugs for Neglected Diseases Initiative
ClinicalTrials.gov Identifier:	NCT00523965 History of Changes
Other Study ID Numbers:	VLCombo 07
Study First Received:	August 31, 2007
Last Updated:	May 25, 2010
Health Authority:	India: Ministry of Health

Keywords provided by Banaras Hindu University:

Kala-azar
miltefosine
liposomal amphotericin B

Additional relevant MeSH terms:

Leishmaniasis
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Amphotericin B
Paromomycin
Liposomal amphotericin B
Amphotericin B, deoxycholate drug combination
Miltefosine

Deoxycholic Acid
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Bacterial Agents
Cholagogues and Choleretics
Gastrointestinal Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012