Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

Detalhes bibliográficos
Autor(a) principal: Romero, Gustavo Adolfo Sierra
Data de Publicação: 2017
Outros Autores: Costa, Dorcas Lamounier, Costa, Carlos Henrique Nery, Almeida, Roque Pacheco de, Melo, Enaldo Viera de, Carvalho, Sílvio Fernando Guimarães de, Rabello, Ana Lúcia Teles, Carvalho, Andréa Lucchesi de, Sousa, Anastácio de Queiroz, Leite, Robério Dias, Lima, Simone Soares, Amaral, Thais Alves, Alves, Fabiana Piovesan, Rode, Joelle
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/25996
Resumo: Universidade de Brasília. Núcleo de Medicina Tropical Brasília, DF, Brasil
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spelling Romero, Gustavo Adolfo SierraCosta, Dorcas LamounierCosta, Carlos Henrique NeryAlmeida, Roque Pacheco deMelo, Enaldo Viera deCarvalho, Sílvio Fernando Guimarães deRabello, Ana Lúcia TelesCarvalho, Andréa Lucchesi deSousa, Anastácio de QueirozLeite, Robério DiasLima, Simone SoaresAmaral, Thais AlvesAlves, Fabiana PiovesanRode, Joelle2018-04-20T18:24:28Z2018-04-20T18:24:28Z2017ROMERO, Gustavo Adolfo Sierra et al. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. , v. 11, n. 6, art. e0005706, 2017.1935-2735https://www.arca.fiocruz.br/handle/icict/2599610.1371/journal.pntd.0005706engPublic Library of ScienceAmphotericin B/efeitos colateraisAmphotericin B/adverse effectsDrug Therapy, Combination/methodsLeishmaniasis, Visceral/drug therapyMeglumine/adverse effectsOrganometallic Compounds/therapeutic useTreatment OutcomeEfficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trialinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de Brasília. Núcleo de Medicina Tropical Brasília, DF, BrasilUniversidade Federal do Piauí. Hospital de Doenças Tropicais Natan Portela, Teresina, PI, BrasilUniversidade Federal do Piauí. Hospital de Doenças Tropicais Natan Portela, Teresina, PI, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilUniversidade Estadual de Montes Claros. Hospital Universitário Clemente de Faria. Departamento de Doenças Infecciosas. Montes Claros, MG, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Pesquisa Clínica, e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, BrasilFundação Hospitalar do Estado de Minas Gerais. Hospital Infantil João Paulo II. Belo Horizonte, MG, BrasilUniversidade Federal do Ceará. Hospital São José de Doenças Infecciosas. Fortaleza, CE, BrasilUniversidade Federal do Ceará. Hospital São José de Doenças Infecciosas. Fortaleza, CE, BrasilUniversidade Federal do Piauí. Hospital Infantil Lucídio Portela. Teresina, PI, BrasilFundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Plataforma de Pesquisa Clínica. Rio de Janeiro, RJ, BrasilDrugs for Neglected Diseases initiative. Geneva, Switzerland.Drugs for Neglected Diseases initiative. Rio de Janeiro, RJ, BrasilBACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. RESULTS: 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). CONCLUSIONS: Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/25996/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALEfficacy and safety of available treatments for visceral .pdfEfficacy and safety of available treatments for visceral .pdfapplication/pdf11005490https://www.arca.fiocruz.br/bitstream/icict/25996/2/Efficacy%20and%20safety%20of%20available%20treatments%20for%20visceral%20.pdfff4e05f7e1e285e1e33cb8a9eeab4905MD52TEXTEfficacy and safety of available treatments for visceral .pdf.txtEfficacy and safety of available treatments for visceral .pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
title Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
spellingShingle Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
Romero, Gustavo Adolfo Sierra
Amphotericin B/efeitos colaterais
Amphotericin B/adverse effects
Drug Therapy, Combination/methods
Leishmaniasis, Visceral/drug therapy
Meglumine/adverse effects
Organometallic Compounds/therapeutic use
Treatment Outcome
title_short Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
title_full Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
title_fullStr Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
title_full_unstemmed Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
title_sort Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial
author Romero, Gustavo Adolfo Sierra
author_facet Romero, Gustavo Adolfo Sierra
Costa, Dorcas Lamounier
Costa, Carlos Henrique Nery
Almeida, Roque Pacheco de
Melo, Enaldo Viera de
Carvalho, Sílvio Fernando Guimarães de
Rabello, Ana Lúcia Teles
Carvalho, Andréa Lucchesi de
Sousa, Anastácio de Queiroz
Leite, Robério Dias
Lima, Simone Soares
Amaral, Thais Alves
Alves, Fabiana Piovesan
Rode, Joelle
author_role author
author2 Costa, Dorcas Lamounier
Costa, Carlos Henrique Nery
Almeida, Roque Pacheco de
Melo, Enaldo Viera de
Carvalho, Sílvio Fernando Guimarães de
Rabello, Ana Lúcia Teles
Carvalho, Andréa Lucchesi de
Sousa, Anastácio de Queiroz
Leite, Robério Dias
Lima, Simone Soares
Amaral, Thais Alves
Alves, Fabiana Piovesan
Rode, Joelle
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Romero, Gustavo Adolfo Sierra
Costa, Dorcas Lamounier
Costa, Carlos Henrique Nery
Almeida, Roque Pacheco de
Melo, Enaldo Viera de
Carvalho, Sílvio Fernando Guimarães de
Rabello, Ana Lúcia Teles
Carvalho, Andréa Lucchesi de
Sousa, Anastácio de Queiroz
Leite, Robério Dias
Lima, Simone Soares
Amaral, Thais Alves
Alves, Fabiana Piovesan
Rode, Joelle
dc.subject.other.pt_BR.fl_str_mv Amphotericin B/efeitos colaterais
topic Amphotericin B/efeitos colaterais
Amphotericin B/adverse effects
Drug Therapy, Combination/methods
Leishmaniasis, Visceral/drug therapy
Meglumine/adverse effects
Organometallic Compounds/therapeutic use
Treatment Outcome
dc.subject.en.pt_BR.fl_str_mv Amphotericin B/adverse effects
Drug Therapy, Combination/methods
Leishmaniasis, Visceral/drug therapy
Meglumine/adverse effects
Organometallic Compounds/therapeutic use
Treatment Outcome
description Universidade de Brasília. Núcleo de Medicina Tropical Brasília, DF, Brasil
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-04-20T18:24:28Z
dc.date.available.fl_str_mv 2018-04-20T18:24:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv ROMERO, Gustavo Adolfo Sierra et al. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. , v. 11, n. 6, art. e0005706, 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/25996
dc.identifier.issn.pt_BR.fl_str_mv 1935-2735
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0005706
identifier_str_mv ROMERO, Gustavo Adolfo Sierra et al. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. , v. 11, n. 6, art. e0005706, 2017.
1935-2735
10.1371/journal.pntd.0005706
url https://www.arca.fiocruz.br/handle/icict/25996
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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