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

NCT ID: NCT01310738

Last Updated: 2017-09-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 378 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-02-28

Brief Summary

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.

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.

Conditions

Visceral Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Meglumine antimoniate

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

Group Type: ACTIVE_COMPARATOR

Antimoniate of N-methylglucamine

Intervention Type: DRUG

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

Liposomal Amphotericin B

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

Group Type: EXPERIMENTAL

Liposomal amphotericin B

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

amphotericin B deoxycholate

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Liposomal amphotericin B

Intervention Type: DRUG

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

Antimoniate of N-methylglucamine

Intervention Type: DRUG

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

Interventions

Antimoniate of N-methylglucamine

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

Intervention Type: DRUG

amphotericin B deoxycholate

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

Intervention Type: DRUG

Liposomal amphotericin B

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

Intervention Type: DRUG

Liposomal amphotericin B

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

Intervention Type: DRUG

Antimoniate of N-methylglucamine

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

Intervention Type: DRUG

Other Intervention Names

Glucantime; Fungizone; Anforicin B; AmBisome; AmBisome; Glucantime

Eligibility 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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: collaborator

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

University of Brasilia

OTHER

Sponsor Role: lead

Responsible Party

Gustavo Adolfo Sierra Romero

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlos HN Costa, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of Piaui

Dorcas L Costa, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of Piaui

Ana LT Rabello, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Centro de Pesquisas Rene Rachou - Fiocruz - Minas Gerais

Silvio FG de Carvalho, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Montes Claros State University - Unimontes

Andrea L de Carvalho, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Infantil Joao Paulo II - FHEMIG

Roque P de Almeida, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of Sergipe

Fabiana P Alves, MD PhD

Role: STUDY_DIRECTOR

Drugs for Neglected Diseases

Gustavo AS Romero, MD PhD

Role: STUDY_CHAIR

University of Brasilia

Robério D Leite, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital São José de Doenças Infecciosas, Secretaria de Saúde do Estado do Ceará.

Locations

Hospital Universitário da Universidade Federal de Sergipe

Sergipe, Aracaju, Brazil

Hospital São José de Doenças Infecciosas

Fortaleza, Ceará, Brazil

Hospital Infantil João Paulo II - FHEMIG

Belo Horizonte, Minas Gerais, Brazil

Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros

Montes Claros, Minas Gerais, Brazil

Hospital de Doencas Infecto Contagiosas - HDIC

Teresina, Piauí, Brazil

Countries

Brazil

References

Romero GAS, Costa DL, Costa CHN, de Almeida RP, de Melo EV, de Carvalho SFG, Rabello A, de Carvalho AL, Sousa AQ, Leite RD, Lima SS, Amaral TA, Alves FP, Rode J; Collaborative LVBrasil Group. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005706. doi: 10.1371/journal.pntd.0005706. eCollection 2017 Jun.

Reference Type: RESULT

PMID: 28662034 (View on PubMed)

Other Identifiers

559819/2010-2

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

108042500

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CAAE 0973.1.000.245-10

Identifier Type: OTHER

Identifier Source: secondary_id

LVBrasil_2007

Identifier Type: -

Identifier Source: org_study_id