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

NCT ID: NCT00371995

Last Updated: 2011-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2010-02-28

Brief 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.

Detailed 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

Conditions

Visceral Leishmaniasis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

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)

Group Type: EXPERIMENTAL

Liposomal amphotericin B and Miltefosine

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

Other Intervention Names

AmBisome and Impavido

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rajendra Memorial Research Institute of Medical Sciences

OTHER

Sponsor Role: collaborator

Banaras Hindu University

OTHER

Sponsor Role: lead

Responsible Party

Banaras Hdindu University

Principal Investigators

Shyam Sundar, MD

Role: PRINCIPAL_INVESTIGATOR

Banaras Hindu University

Prabhat K Sinha, MD

Role: PRINCIPAL_INVESTIGATOR

Rajendra Memorial Research Institute of Medical Sciences

Locations

Kala-azar Medical Research Center

Muzaffarpur, Bihar, India

Rajendra Memorial Research Institute of Medical Sciences

Patna, Bihar, India

Countries

India

References

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/j.trstmh.2010.10.008. Epub 2010 Dec 3.

Reference Type: RESULT

PMID: 21129762 (View on PubMed)

Other Identifiers

LEI PDE 06 03

Identifier Type: -

Identifier Source: org_study_id