Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil (LVBrasil)

University of Brasilia

Status and phase: Terminated; Phase 4

Conditions: Visceral Leishmaniasis

Treatments: Drug: amphotericin B deoxycholate; Drug: Liposomal amphotericin B; Drug: Antimoniate of N-methylglucamine

Study type: Interventional

Funder types: Other

Identifiers

NCT01310738

108042500 (Other Grant/Funding Number)

559819/2010-2 (Other Grant/Funding Number)

CAAE 0973.1.000.245-10 (Other Identifier)

LVBrasil_2007

Details and patient eligibility

About

This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.

Full description

Visceral leishmaniasis is a relevant public health problem in Brazil with approximately 3500 cases registered every year. Eight percent lethality rate has been observed during the past decade in spite of free of charge availability of antileishmanial drugs supplied by the public health system.

The present study was designed as a phase IV, multicentric, open label, active controlled clinical trial targeted to visceral leishmaniasis adult and pediatric cases.

The current drugs approved for visceral leishmaniasis treatment in Brazil will be compared in four treatment groups: meglumine antimoniate, amphotericin B deoxycholate, liposomal amphotericin B and a combination of single dose of liposomal amphotericin B plus meglumine antimoniate. Meglumine antimoniate treated patients will constitute the active control group.

Drugs will be compared based on the cure rate observed after six months follow-up.

The study arm submitted to treatment with Amphotericin B deoxycholate was suspended in September 2012.

Enrollment: 378 patients

Sex: All

Ages: 6 months to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• patients with visceral leishmaniasis characterized by fever plus hepatomegaly or splenomegaly with at least one positive result in the following laboratory tests:
• direct observation of leishmania amastigotes in bone marrow smear
• leishmania in vitro culture from bone marrow aspirates
• leishmania kDNA amplification by PCR in bone marrow or peripheral blood samples
• rK39 immunochromatographic rapid test performed on serum sample

Exclusion criteria

• pregnancy
• HIV infection
• chronic diseases such as diabetes mellitus,kidney, liver or cardiac diseases, schistosomiasis, malaria or tuberculosis
• immune disorders or use of drugs which interferes with the immune response
• treatment with drugs with increased risk for toxicity associated with the study drugs
• exposure to antileishmanial drugs during the past six months
• I.V. drug users
• episodes of visceral leishmaniasis relapse
• hypersensibility to the study drugs
• difficulties for accomplishing the follow-up schedule
• any of the following clinical signs of laboratory abnormalities: hepatic encephalopathy, generalized edema, toxemic individuals, severe malnutrition, jaundice, abnormal serum creatinine, bilirubin, INR > 2,0, platelet count < 20000/mm3

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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378 participants in 4 patient groups

Meglumine antimoniate

Active Comparator group

Description:

Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.

Treatment:

Drug: Antimoniate of N-methylglucamine

Drug: Antimoniate of N-methylglucamine

Liposomal Amphotericin B

Experimental group

Description:

Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.

Treatment:

Drug: Liposomal amphotericin B

Drug: Liposomal amphotericin B

Amphotericin B

Experimental group

Description:

Amphotericin B deoxycholate 1mg/kg/d I.V. for 14 consecutive days. This arm was suspended in September 19th, 2012, because of a relevant excess of adverse events and serious adverse events associated with this experimental intervention in comparison with the active comparator and the other two experimental arms. The suspension of this study arm was supported by a DSMB statement.

Treatment:

Drug: amphotericin B deoxycholate

Combination therapy

Experimental group

Description:

Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10.

Treatment:

Drug: Liposomal amphotericin B

Drug: Antimoniate of N-methylglucamine

Drug: Antimoniate of N-methylglucamine

Drug: Liposomal amphotericin B