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.)
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01310738
First received: March 7, 2011
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: November 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.

  Eligibility

Ages Eligible for Study:   6 Months to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01310738

Locations
Brazil
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
Investigators
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

No publications provided

Responsible Party: Gustavo Adolfo Sierra Romero, Professor, University of Brasilia
ClinicalTrials.gov Identifier: NCT01310738     History of Changes
Other Study ID Numbers: LVBrasil_2007, 559819/2010-2, 108042500, CAAE 0973.1.000.245-10
Study First Received: March 7, 2011
Last Updated: June 4, 2014
Health Authority: Brazil: Ministry of Health

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

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Amphotericin B
Liposomal amphotericin B
Amphotericin B, deoxycholate drug combination
Meglumine antimoniate
Deoxycholic Acid
Meglumine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Antifungal Agents
Cholagogues and Choleretics
Gastrointestinal Agents
Contrast Media
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 27, 2014