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

This study has been terminated.
(DSMB recommendation based on programmed interim analysis.)
Ministry of Health, Brazil
Drugs for Neglected Diseases
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
Gustavo Adolfo Sierra Romero, University of Brasilia Identifier:
First received: March 7, 2011
Last updated: January 20, 2016
Last verified: January 2016
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.

Condition Intervention Phase
Visceral Leishmaniasis
Drug: Antimoniate of N-methylglucamine
Drug: amphotericin B deoxycholate
Drug: Liposomal amphotericin B
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil

Resource links provided by NLM:

Further study details as provided by University of Brasilia:

Primary Outcome Measures:
  • Cure rate [ Time Frame: 6 month ]
    Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up.

Secondary Outcome Measures:
  • Improvement rate [ Time Frame: 30 days ]
    Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction.

  • Relapse rate [ Time Frame: (6 months post treatment) After treatment until the sixth month of follow-up ]
    Reappearing of signs and symptoms after any improvement observed after treatment, during the six months follow-up period.

  • Serious adverse events rate [ Time Frame: During (day one) and within the six months follow-up ]
    Rate of adverse events defined as conditions which fulfilled any of the following: results in death, is life threatening, requires inpatient hospitalization or prolongs hospitalization, results in persistent or significant disability/incapacity, causes a congenital anomaly or birth defect or it is considered as a important medical event for the responsible clinician.

  • Adverse event rate and intensity [ Time Frame: During (day one) treatment and within the six months follow-up ]
    Cumulative rate of any adverse event, including clinical, laboratory and electrocardiographic abnormalities observed within the treatment and follow-up periods. All adverse events will be graded using an adapted ACTG 0-4 scale.

Enrollment: 380
Study Start Date: February 2011
Study Completion Date: February 2015
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Meglumine antimoniate
Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.
Drug: Antimoniate of N-methylglucamine
Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.
Other Name: Glucantime
Experimental: Liposomal Amphotericin B
Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.
Drug: Liposomal amphotericin B
3mg/kg/d, I.V. for 7 consecutive days.
Other Name: AmBisome
Experimental: Amphotericin B
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.
Drug: amphotericin B deoxycholate
1mg/kg/d, I.V. for 14 consecutive days.
Other Names:
  • Fungizone
  • Anforicin B
Experimental: Combination therapy
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.
Drug: Liposomal amphotericin B
10mg/kg/d, I.V. single dose.
Other Name: AmBisome
Drug: Antimoniate of N-methylglucamine
20mg/kg/d of pentavalent antimonial I.V. for 10 days
Other Name: Glucantime

Detailed 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.


Ages Eligible for Study:   6 Months to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01310738

Hospital Universitário da Universidade Federal de Sergipe
Sergipe, Aracaju, Brazil, 49060-100
Hospital São José de Doenças Infecciosas
Fortaleza, Ceará, Brazil, 60455610
Hospital Infantil João Paulo II - FHEMIG
Belo Horizonte, Minas Gerais, Brazil, 30130-110
Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros
Montes Claros, Minas Gerais, Brazil, 39401-002
Hospital de Doencas Infecto Contagiosas - HDIC
Teresina, Piaui, Brazil, 64001450
Sponsors and Collaborators
University of Brasilia
Ministry of Health, Brazil
Drugs for Neglected Diseases
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Principal Investigator: Carlos HN Costa, MD PhD Federal University of Piaui
Principal Investigator: Dorcas L Costa, MD PhD Federal University of Piaui
Principal Investigator: Ana LT Rabello, MD PhD Centro de Pesquisas Rene Rachou - Fiocruz - Minas Gerais
Principal Investigator: Silvio FG de Carvalho, MD PhD Montes Claros State University - Unimontes
Principal Investigator: Andrea L de Carvalho, MD Hospital Infantil Joao Paulo II - FHEMIG
Principal Investigator: Roque P de Almeida, MD PhD Federal University of Sergipe
Study Director: Fabiana P Alves, MD PhD Drugs for Neglected Diseases
Study Chair: Gustavo AS Romero, MD PhD University of Brasilia
Principal Investigator: Robério D Leite, MD, PhD Hospital São José de Doenças Infecciosas, Secretaria de Saúde do Estado do Ceará.
  More Information

Responsible Party: Gustavo Adolfo Sierra Romero, Professor, University of Brasilia Identifier: NCT01310738     History of Changes
Other Study ID Numbers: LVBrasil_2007
559819/2010-2 ( Other Grant/Funding Number: CNPq - Brazil )
108042500 ( Other Grant/Funding Number: Finaciadora de Estudos e Projetos - FINEP - Brazil )
CAAE 0973.1.000.245-10 ( Other Identifier: Brazilian National Ethics Council )
Study First Received: March 7, 2011
Last Updated: January 20, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Brasilia:
Visceral leishmaniasis
Leishmania infantum
Leishmania chagasi

Additional relevant MeSH terms:
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Meglumine antimoniate
Liposomal amphotericin B
Amphotericin B
Amphotericin B, deoxycholate drug combination
Deoxycholic Acid
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antifungal Agents
Anti-Bacterial Agents
Cholagogues and Choleretics
Gastrointestinal Agents processed this record on April 28, 2017