Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar

Visceral Leishmaniasis Clinical Trial

Official title:

The Efficacy and Safety of a Short Course of Miltefosine and Liposomal Amphotericin B for Visceral Leishmaniasis in India

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00371995
• Other study ID #: LEI PDE 06 03
• Status: Completed
• Phase: Phase 2
• First received: September 5, 2006
• Last updated: June 21, 2011
• Start date: October 2007
• Est. completion date: February 2010

Study information

• Verified date: September 2008
• Source: Banaras Hindu University
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Miltefosine and liposomal amphotericin B (AmBisome) are approved drugs for visceral leishmaniasis. In this study both drugs will be given in a sequential manner. AmBisome will be given on day 1, followed by Miltefosine for 14 days. Final Cure will be evaluated at six months.

Description:

Methodology Multicenter trial, eligible patients will be treated with Liposomal amphotericin B (5 mg/kg) on day 1 and then with miltefosine capsules for 14 days (days 2-15).

At two weeks after the end of treatment the initial cure (clinical and parasitological cure) and the clinical response will be determined. If initial cure is observed, a patient will be evaluated after a 6 months (after end of treatment) follow up period for final clinical cure.

Number of patients planned Total number of patients planned: 150 patients at both centers combined. 75 pediatric (2-11 years); 75 adult (12-65 years).

Lack of suitability for the trial:

• Post Kala-azar Dermal Leishmaniasis (PKDL)

• Concomitant treatment with other anti-leishmanial drugs

• Any condition which compromises ability to comply with the study procedures

Administrative reasons:

• Any condition or situation that compromises compliance with study procedures including follow-up visit Study medication, dose and mode of administration Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg.

Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)

Dosage:

1. weighing ≥ 25 kg: 100 mg miltefosine daily as one capsule (50 mg) in the morning and one capsule in the evening, after meals for 14 days.

2. weighing < 25 kg: 50 mg miltefosine daily as one capsule (50 mg) in the morning, after meals for 14 days. Parameter for evaluation

• Final cure rate (initial parasite cure and clinical assessment at six month EOT)

• Initial parasitological cure rate (based on splenic aspirates or Bone marrow aspirate)

• Clinical response at end of treatment (clinical assessment)

• Adverse events

Statistical methods

• Calculation of cure rate with 95% and 90% lower confidence limit according to Clopper Pearson

• Calculation of overall incidence of adverse events

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: February 2010
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male and female age between 2 and 65 years (inclusive)

• Parasites visualized on splenic aspiration

• Signs and symptoms compatible with visceral leishmaniasis (e.g. fever, splenomegaly, anaemia, weight loss, leucopenia, thrombocytopenia)

• Confirmed diagnosis of VL by visualization of parasites on splenic/bone marrow aspirate

• Fever for at least 2 weeks

• Written informed consent from the patient/or from parent or guardian if under 18 years old

Exclusion Criteria:

• Hemoglobin < 6 g/dl

• White blood cell count < 1000/mm3

• Platelets <50,000

• Prothrombin time > 5 sec above control

• ASAT > 3 times the upper limit of normal

• Serum creatinine or BUN > 1.5 times the upper limit of normal

• Malaria

• Tuberculosis

• HIV positive serology

• Lactation, pregnancy

• Refusing contraception method during treatment period plus 3 months

• Any medical condition(s) that upon judgment of physician may affect the safety of the patient when treated with study drugs

• Any concomitant drug that is nephrotoxic

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Visceral Leishmaniasis

Intervention

Drug:
• Liposomal amphotericin B and Miltefosine
Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)

Locations

Country	Name	City	State
India	Kala-azar Medical Research Center	Muzaffarpur	Bihar
India	Rajendra Memorial Research Institute of Medical Sciences	Patna	Bihar

Sponsors (2)

Lead Sponsor	Collaborator
Banaras Hindu University	Rajendra Memorial Research Institute of Medical Sciences

Country where clinical trial is conducted

India, 

References & Publications (1)

Sundar S, Sinha PK, Verma DK, Kumar N, Alam S, Pandey K, Kumari P, Ravidas V, Chakravarty J, Verma N, Berman J, Ghalib H, Arana B. Ambisome plus miltefosine for Indian patients with kala-azar. Trans R Soc Trop Med Hyg. 2011 Feb;105(2):115-7. doi: 10.1016/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final Cure six months after the end of treatment		1 year	Yes