Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial
- Autores
- Bosch Nicolau, Pau; Fernández, Marisa Liliana; Sulleiro Igual, Elena; Villar, Juan Carlos; Perez Molina, José A.; Correa Oliveira, Rodrigo; Sosa Estani, Sergio Alejandro; Sánchez Montalvá, Adrián; Bangher, María del Carmen; Moreira, Otacilio C.; Salvador, Fernando; Mota Ferreira, Ariela; Eloi Santos, Silvana Maria; Serre Delcor, Núria; Ramírez, Juan Carlos; Silgado, Aroa; Oliveira, Inés; Martín, Oihane; Aznar, Maria Luisa; Ribeiro, Antonio Luiz P.; Almeida, Paulo Emilio Clementino; Chamorro Tojeiro, Sandra; Espinosa Pereiro, Juan; de Paula, Alfredo Mauricio Batista; Váquiro Herrera, Eliana; Tur, Carmen; Molina, Israel
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. Methods The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. Findings From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). Interpretation Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. Funding European Community's 7th Framework Programme.
Fil: Bosch Nicolau, Pau. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Fernández, Marisa Liliana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Sulleiro Igual, Elena. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Villar, Juan Carlos. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Perez Molina, José A.. Instituto de Salud Carlos III; España. Hospital Universitario Ramón y Cajal IRYCIS; España
Fil: Correa Oliveira, Rodrigo. Fundación Oswaldo Cruz; Brasil
Fil: Sosa Estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez Montalvá, Adrián. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Bangher, María del Carmen. Instituto de Cardiología de Corrientes Juana Francisca Cabral; Argentina
Fil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; Brasil
Fil: Salvador, Fernando. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Mota Ferreira, Ariela. Universidade Estadual de Montes Claros; Brasil
Fil: Eloi Santos, Silvana Maria. Universidade Federal de Minas Gerais; Brasil
Fil: Serre Delcor, Núria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Ramírez, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Silgado, Aroa. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Oliveira, Inés. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Martín, Oihane. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Aznar, Maria Luisa. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Ribeiro, Antonio Luiz P.. Universidade Federal de Minas Gerais; Brasil
Fil: Almeida, Paulo Emilio Clementino. Universidade Estadual de Montes Claros; Brasil
Fil: Chamorro Tojeiro, Sandra. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: Espinosa Pereiro, Juan. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España
Fil: de Paula, Alfredo Mauricio Batista. Universidade Estadual de Montes Claros; Brasil
Fil: Váquiro Herrera, Eliana. Fundación Cardioinfantil. Instituto de Cardiología; Colombia
Fil: Tur, Carmen. Hospital Universitari Vall D'hebron; España. University College London; Estados Unidos
Fil: Molina, Israel. Hospital Universitari Vall D'hebron; España. Universitat Autònoma de Barcelona; España - Materia
-
CHAGAS DISEASE
TRYPANOCIDAL DRUGS
CLINICAL TRIALS
BENZNIDAZOLE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/266038
Ver los metadatos del registro completo
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Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trialBosch Nicolau, PauFernández, Marisa LilianaSulleiro Igual, ElenaVillar, Juan CarlosPerez Molina, José A.Correa Oliveira, RodrigoSosa Estani, Sergio AlejandroSánchez Montalvá, AdriánBangher, María del CarmenMoreira, Otacilio C.Salvador, FernandoMota Ferreira, ArielaEloi Santos, Silvana MariaSerre Delcor, NúriaRamírez, Juan CarlosSilgado, AroaOliveira, InésMartín, OihaneAznar, Maria LuisaRibeiro, Antonio Luiz P.Almeida, Paulo Emilio ClementinoChamorro Tojeiro, SandraEspinosa Pereiro, Juande Paula, Alfredo Mauricio BatistaVáquiro Herrera, ElianaTur, CarmenMolina, IsraelCHAGAS DISEASETRYPANOCIDAL DRUGSCLINICAL TRIALSBENZNIDAZOLEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. Methods The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. Findings From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). Interpretation Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. Funding European Community's 7th Framework Programme.Fil: Bosch Nicolau, Pau. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Fernández, Marisa Liliana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Sulleiro Igual, Elena. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Villar, Juan Carlos. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Perez Molina, José A.. Instituto de Salud Carlos III; España. Hospital Universitario Ramón y Cajal IRYCIS; EspañaFil: Correa Oliveira, Rodrigo. Fundación Oswaldo Cruz; BrasilFil: Sosa Estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez Montalvá, Adrián. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Bangher, María del Carmen. Instituto de Cardiología de Corrientes Juana Francisca Cabral; ArgentinaFil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; BrasilFil: Salvador, Fernando. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Mota Ferreira, Ariela. Universidade Estadual de Montes Claros; BrasilFil: Eloi Santos, Silvana Maria. Universidade Federal de Minas Gerais; BrasilFil: Serre Delcor, Núria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Ramírez, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Silgado, Aroa. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Oliveira, Inés. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Martín, Oihane. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Aznar, Maria Luisa. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Ribeiro, Antonio Luiz P.. Universidade Federal de Minas Gerais; BrasilFil: Almeida, Paulo Emilio Clementino. Universidade Estadual de Montes Claros; BrasilFil: Chamorro Tojeiro, Sandra. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: Espinosa Pereiro, Juan. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; EspañaFil: de Paula, Alfredo Mauricio Batista. Universidade Estadual de Montes Claros; BrasilFil: Váquiro Herrera, Eliana. Fundación Cardioinfantil. Instituto de Cardiología; ColombiaFil: Tur, Carmen. Hospital Universitari Vall D'hebron; España. University College London; Estados UnidosFil: Molina, Israel. Hospital Universitari Vall D'hebron; España. Universitat Autònoma de Barcelona; EspañaElsevier Science Inc.2024-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266038Bosch Nicolau, Pau; Fernández, Marisa Liliana; Sulleiro Igual, Elena; Villar, Juan Carlos; Perez Molina, José A.; et al.; Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial; Elsevier Science Inc.; Lancet Infectious Diseases; 24; 4; 1-2024; 386-3941473-3099CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S1473-3099(23)00629-1info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1473309923006291info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:38Zoai:ri.conicet.gov.ar:11336/266038instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:39.261CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| title |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| spellingShingle |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial Bosch Nicolau, Pau CHAGAS DISEASE TRYPANOCIDAL DRUGS CLINICAL TRIALS BENZNIDAZOLE |
| title_short |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| title_full |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| title_fullStr |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| title_full_unstemmed |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| title_sort |
Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial |
| dc.creator.none.fl_str_mv |
Bosch Nicolau, Pau Fernández, Marisa Liliana Sulleiro Igual, Elena Villar, Juan Carlos Perez Molina, José A. Correa Oliveira, Rodrigo Sosa Estani, Sergio Alejandro Sánchez Montalvá, Adrián Bangher, María del Carmen Moreira, Otacilio C. Salvador, Fernando Mota Ferreira, Ariela Eloi Santos, Silvana Maria Serre Delcor, Núria Ramírez, Juan Carlos Silgado, Aroa Oliveira, Inés Martín, Oihane Aznar, Maria Luisa Ribeiro, Antonio Luiz P. Almeida, Paulo Emilio Clementino Chamorro Tojeiro, Sandra Espinosa Pereiro, Juan de Paula, Alfredo Mauricio Batista Váquiro Herrera, Eliana Tur, Carmen Molina, Israel |
| author |
Bosch Nicolau, Pau |
| author_facet |
Bosch Nicolau, Pau Fernández, Marisa Liliana Sulleiro Igual, Elena Villar, Juan Carlos Perez Molina, José A. Correa Oliveira, Rodrigo Sosa Estani, Sergio Alejandro Sánchez Montalvá, Adrián Bangher, María del Carmen Moreira, Otacilio C. Salvador, Fernando Mota Ferreira, Ariela Eloi Santos, Silvana Maria Serre Delcor, Núria Ramírez, Juan Carlos Silgado, Aroa Oliveira, Inés Martín, Oihane Aznar, Maria Luisa Ribeiro, Antonio Luiz P. Almeida, Paulo Emilio Clementino Chamorro Tojeiro, Sandra Espinosa Pereiro, Juan de Paula, Alfredo Mauricio Batista Váquiro Herrera, Eliana Tur, Carmen Molina, Israel |
| author_role |
author |
| author2 |
Fernández, Marisa Liliana Sulleiro Igual, Elena Villar, Juan Carlos Perez Molina, José A. Correa Oliveira, Rodrigo Sosa Estani, Sergio Alejandro Sánchez Montalvá, Adrián Bangher, María del Carmen Moreira, Otacilio C. Salvador, Fernando Mota Ferreira, Ariela Eloi Santos, Silvana Maria Serre Delcor, Núria Ramírez, Juan Carlos Silgado, Aroa Oliveira, Inés Martín, Oihane Aznar, Maria Luisa Ribeiro, Antonio Luiz P. Almeida, Paulo Emilio Clementino Chamorro Tojeiro, Sandra Espinosa Pereiro, Juan de Paula, Alfredo Mauricio Batista Váquiro Herrera, Eliana Tur, Carmen Molina, Israel |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
CHAGAS DISEASE TRYPANOCIDAL DRUGS CLINICAL TRIALS BENZNIDAZOLE |
| topic |
CHAGAS DISEASE TRYPANOCIDAL DRUGS CLINICAL TRIALS BENZNIDAZOLE |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Background Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. Methods The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. Findings From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). Interpretation Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. Funding European Community's 7th Framework Programme. Fil: Bosch Nicolau, Pau. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Fernández, Marisa Liliana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina Fil: Sulleiro Igual, Elena. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España Fil: Villar, Juan Carlos. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Perez Molina, José A.. Instituto de Salud Carlos III; España. Hospital Universitario Ramón y Cajal IRYCIS; España Fil: Correa Oliveira, Rodrigo. Fundación Oswaldo Cruz; Brasil Fil: Sosa Estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sánchez Montalvá, Adrián. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Bangher, María del Carmen. Instituto de Cardiología de Corrientes Juana Francisca Cabral; Argentina Fil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; Brasil Fil: Salvador, Fernando. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Mota Ferreira, Ariela. Universidade Estadual de Montes Claros; Brasil Fil: Eloi Santos, Silvana Maria. Universidade Federal de Minas Gerais; Brasil Fil: Serre Delcor, Núria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España Fil: Ramírez, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Silgado, Aroa. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Oliveira, Inés. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España Fil: Martín, Oihane. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España Fil: Aznar, Maria Luisa. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España Fil: Ribeiro, Antonio Luiz P.. Universidade Federal de Minas Gerais; Brasil Fil: Almeida, Paulo Emilio Clementino. Universidade Estadual de Montes Claros; Brasil Fil: Chamorro Tojeiro, Sandra. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: Espinosa Pereiro, Juan. Instituto de Salud Carlos III; España. Universitat Autònoma de Barcelona; España Fil: de Paula, Alfredo Mauricio Batista. Universidade Estadual de Montes Claros; Brasil Fil: Váquiro Herrera, Eliana. Fundación Cardioinfantil. Instituto de Cardiología; Colombia Fil: Tur, Carmen. Hospital Universitari Vall D'hebron; España. University College London; Estados Unidos Fil: Molina, Israel. Hospital Universitari Vall D'hebron; España. Universitat Autònoma de Barcelona; España |
| description |
Background Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. Methods The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. Findings From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). Interpretation Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. Funding European Community's 7th Framework Programme. |
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2024 |
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2024-01 |
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article |
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http://hdl.handle.net/11336/266038 Bosch Nicolau, Pau; Fernández, Marisa Liliana; Sulleiro Igual, Elena; Villar, Juan Carlos; Perez Molina, José A.; et al.; Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial; Elsevier Science Inc.; Lancet Infectious Diseases; 24; 4; 1-2024; 386-394 1473-3099 CONICET Digital CONICET |
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http://hdl.handle.net/11336/266038 |
| identifier_str_mv |
Bosch Nicolau, Pau; Fernández, Marisa Liliana; Sulleiro Igual, Elena; Villar, Juan Carlos; Perez Molina, José A.; et al.; Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial; Elsevier Science Inc.; Lancet Infectious Diseases; 24; 4; 1-2024; 386-394 1473-3099 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/S1473-3099(23)00629-1 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1473309923006291 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier Science Inc. |
| publisher.none.fl_str_mv |
Elsevier Science Inc. |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269173185511424 |
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13.13397 |