Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil
Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
  • Phase

    Phase 4
  • Study Type

  • Status

  • Study Participants

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.
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.
Study Started
Feb 28
Primary Completion
Oct 31
Study Completion
Feb 28
Last Update
Sep 05

Drug Antimoniate of N-methylglucamine

Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.

  • Other names: Glucantime

Drug amphotericin B deoxycholate

1mg/kg/d, I.V. for 14 consecutive days.

  • Other names: Fungizone, Anforicin B

Drug Liposomal amphotericin B

3mg/kg/d, I.V. for 7 consecutive days.

  • Other names: AmBisome

Drug Liposomal amphotericin B

10mg/kg/d, I.V. single dose.

  • Other names: AmBisome

Drug Antimoniate of N-methylglucamine

20mg/kg/d of pentavalent antimonial I.V. for 10 days

  • Other names: Glucantime

Meglumine antimoniate Active Comparator

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

Liposomal Amphotericin B Experimental

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

Amphotericin B Experimental

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.

Combination therapy Experimental

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.


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:

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
No Results Posted