Clinical trial NCT00523965: Combination Therapy in Indian Visceral Leishmaniasis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leishmaniasis, Visceral
Keywords: Kala-azar
miltefosine
liposomal amphotericin B
Lead sponsor: Banaras Hindu University
Sponsor class: OTHER
Collaborators: name: Drugs for Neglected Diseases
name: Rajendra Memorial Research Institute of Medical Sciences
First posted: 2007-09-03
Enrollment: 624
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Final cure at six month follow up
timeFrame: 18 months
measure: Cure at six month follow up
timeFrame: 12 months
Secondary outcomes:
measure: Initial cure at the end of treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Muzaffarpur
country: India
facility: Kala-azar Medical Research Center
state: Bihar
Study officials:
affiliation: Institute of Medical Sciences, Banaras HIndu University
name: Shyam Sundar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rajendra Memorial Research Insititute of Medical Sciences
name: P K Sinha, MD
role: PRINCIPAL_INVESTIGATOR
References: