Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial

Autores
Morillo, Carlos A; Waskin, Hetty; Sosa-Estani, Sergio; Del Carmen Bangher, Maria; Cuneo, Carlos; Milesi, Rodolfo; Mallagray, Marcelo; Apt, Werner; Beloscar, Juan; Gascon, Joaquim; Molina, Israel; Echeverria, Luis E; Colombo, Hugo; Perez-Molina, Jose Antonio; Wyss, Fernando; Meeks, Brandi; Bonilla, Laura R; Gao, Peggy; Wei, Bo; McCarthy, Michael; Yusuf, Salim
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Morillo, Carlos A. McMaster University, Population Health Research Institute; Canadá.
Fil: Waskin, Hetty. Merck Sharp and Dohme Corporation; Estados Unidos.
Fil: Sosa-Estani, Sergio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Del Carmen Bangher, Maria. Instituto de Cardiología de Corrientes "Juana F. Cabral"; Argentina.
Fil: Cuneo, Carlos. Hospital San Bernardo. Prevención Cardiovascular; Salta, Argentina.
Fil: Milesi, Rodolfo. Centro de Diagnóstico y Rehabilitación, Santa Fe, Argentina.
Fil: Mallagray, Marcelo. Sanatorio Nuestra señora del Rosario. Centro de Investigaciones Médicas; Jujuy, Argentina.
Fil: Apt, Werner. Universidad de Chile. Facultad de Médicina. Instituto de Ciencias Biomédicas. Laboratorio Clínico Básico de Parasitología; Chile.
Fil: Beloscar, Juan. Hospital Provincial del Centenario; Rosario, Argentina.
Fil: Gascon, Joaquim. Hospital Clínico de Barcelona. Centro de Investigaciones Sanitarias Internacionales de Barcelona; España.
Fil: Molina, Israel. Universidad Autónoma de Barcelona. Hospital Universitario Vall d'Hebron. Departamento de Enfermedades Infecciosas. Programa del Instituto Catalán de Salud; España.
Fil: Echeverria, Luis E. Fundación Cardiovascular; Colombia.
Fil: Colombo, Hugo. Clínica Privada Colombo; Córdoba, Argentina.
Fil: Perez-Molina, Jose Antonio. Hospital Ramón Cajal. Centro Nacional de Referencias de Enfermedades Tropicales. Departamento de Enfermedades Infecciosas; Madrid, España.
Fil: Wyss, Fernando. Sociedad Centroamericana de Hipertensión Arterial y Prevención Cardiovascular; Guatemala.
Fil: Meeks, Brandi. McMaster University, Population Health Research Institute; Canadá.
Fil: Bonilla, Laura R. McMaster University, Population Health Research Institute; Canadá.
Fil: Gao, Peggy. McMaster University, Population Health Research Institute; Canadá.
Fil: Wei, Bo. Merck Sharp and Dohme Corporation; Estados Unidos.
Fil: McCarthy, Michael. Medimmune, Estados Unidos.
Fil: Yusuf, Salim. McMaster University, Population Health Research Institute; Canadá.
Background: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. Objectives: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. Methods: A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days. Results: Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole. Conclusions: Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480)
Materia
Tripanocidas
Enfermedad de Chagas
Análisis por intención de tratar
Parasitemia
Reacción en Cadena de la Polimerasa
Insuficiencia del Tratamiento
Nivel de accesibilidad
acceso abierto
Condiciones de uso
none
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:Publications/123456789/1448

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oai_identifier_str oai:sgc.anlis.gob.ar:Publications/123456789/1448
network_acronym_str SGCANLIS
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network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS TrialMorillo, Carlos AWaskin, HettySosa-Estani, SergioDel Carmen Bangher, MariaCuneo, CarlosMilesi, RodolfoMallagray, MarceloApt, WernerBeloscar, JuanGascon, JoaquimMolina, IsraelEcheverria, Luis EColombo, HugoPerez-Molina, Jose AntonioWyss, FernandoMeeks, BrandiBonilla, Laura RGao, PeggyWei, BoMcCarthy, MichaelYusuf, SalimTripanocidasEnfermedad de ChagasAnálisis por intención de tratarParasitemiaReacción en Cadena de la PolimerasaInsuficiencia del TratamientoFil: Morillo, Carlos A. McMaster University, Population Health Research Institute; Canadá.Fil: Waskin, Hetty. Merck Sharp and Dohme Corporation; Estados Unidos.Fil: Sosa-Estani, Sergio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Del Carmen Bangher, Maria. Instituto de Cardiología de Corrientes "Juana F. Cabral"; Argentina.Fil: Cuneo, Carlos. Hospital San Bernardo. Prevención Cardiovascular; Salta, Argentina.Fil: Milesi, Rodolfo. Centro de Diagnóstico y Rehabilitación, Santa Fe, Argentina.Fil: Mallagray, Marcelo. Sanatorio Nuestra señora del Rosario. Centro de Investigaciones Médicas; Jujuy, Argentina.Fil: Apt, Werner. Universidad de Chile. Facultad de Médicina. Instituto de Ciencias Biomédicas. Laboratorio Clínico Básico de Parasitología; Chile.Fil: Beloscar, Juan. Hospital Provincial del Centenario; Rosario, Argentina.Fil: Gascon, Joaquim. Hospital Clínico de Barcelona. Centro de Investigaciones Sanitarias Internacionales de Barcelona; España.Fil: Molina, Israel. Universidad Autónoma de Barcelona. Hospital Universitario Vall d'Hebron. Departamento de Enfermedades Infecciosas. Programa del Instituto Catalán de Salud; España.Fil: Echeverria, Luis E. Fundación Cardiovascular; Colombia.Fil: Colombo, Hugo. Clínica Privada Colombo; Córdoba, Argentina.Fil: Perez-Molina, Jose Antonio. Hospital Ramón Cajal. Centro Nacional de Referencias de Enfermedades Tropicales. Departamento de Enfermedades Infecciosas; Madrid, España.Fil: Wyss, Fernando. Sociedad Centroamericana de Hipertensión Arterial y Prevención Cardiovascular; Guatemala.Fil: Meeks, Brandi. McMaster University, Population Health Research Institute; Canadá.Fil: Bonilla, Laura R. McMaster University, Population Health Research Institute; Canadá.Fil: Gao, Peggy. McMaster University, Population Health Research Institute; Canadá.Fil: Wei, Bo. Merck Sharp and Dohme Corporation; Estados Unidos.Fil: McCarthy, Michael. Medimmune, Estados Unidos.Fil: Yusuf, Salim. McMaster University, Population Health Research Institute; Canadá.Background: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. Objectives: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. Methods: A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days. Results: Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole. Conclusions: Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480)2017-02-28info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://sgc.anlis.gob.ar/handle/123456789/144810.1016/j.jacc.2016.12.023Journal of the American College of Cardiologynoneinfo:eu-repo/semantics/openAccessengreponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLIS2025-09-29T14:30:20Zoai:sgc.anlis.gob.ar:Publications/123456789/1448Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-09-29 14:30:20.743Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
dc.title.none.fl_str_mv Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
title Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
spellingShingle Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
Morillo, Carlos A
Tripanocidas
Enfermedad de Chagas
Análisis por intención de tratar
Parasitemia
Reacción en Cadena de la Polimerasa
Insuficiencia del Tratamiento
title_short Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
title_full Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
title_fullStr Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
title_full_unstemmed Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
title_sort Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial
dc.creator.none.fl_str_mv Morillo, Carlos A
Waskin, Hetty
Sosa-Estani, Sergio
Del Carmen Bangher, Maria
Cuneo, Carlos
Milesi, Rodolfo
Mallagray, Marcelo
Apt, Werner
Beloscar, Juan
Gascon, Joaquim
Molina, Israel
Echeverria, Luis E
Colombo, Hugo
Perez-Molina, Jose Antonio
Wyss, Fernando
Meeks, Brandi
Bonilla, Laura R
Gao, Peggy
Wei, Bo
McCarthy, Michael
Yusuf, Salim
author Morillo, Carlos A
author_facet Morillo, Carlos A
Waskin, Hetty
Sosa-Estani, Sergio
Del Carmen Bangher, Maria
Cuneo, Carlos
Milesi, Rodolfo
Mallagray, Marcelo
Apt, Werner
Beloscar, Juan
Gascon, Joaquim
Molina, Israel
Echeverria, Luis E
Colombo, Hugo
Perez-Molina, Jose Antonio
Wyss, Fernando
Meeks, Brandi
Bonilla, Laura R
Gao, Peggy
Wei, Bo
McCarthy, Michael
Yusuf, Salim
author_role author
author2 Waskin, Hetty
Sosa-Estani, Sergio
Del Carmen Bangher, Maria
Cuneo, Carlos
Milesi, Rodolfo
Mallagray, Marcelo
Apt, Werner
Beloscar, Juan
Gascon, Joaquim
Molina, Israel
Echeverria, Luis E
Colombo, Hugo
Perez-Molina, Jose Antonio
Wyss, Fernando
Meeks, Brandi
Bonilla, Laura R
Gao, Peggy
Wei, Bo
McCarthy, Michael
Yusuf, Salim
author2_role 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 Tripanocidas
Enfermedad de Chagas
Análisis por intención de tratar
Parasitemia
Reacción en Cadena de la Polimerasa
Insuficiencia del Tratamiento
topic Tripanocidas
Enfermedad de Chagas
Análisis por intención de tratar
Parasitemia
Reacción en Cadena de la Polimerasa
Insuficiencia del Tratamiento
dc.description.none.fl_txt_mv Fil: Morillo, Carlos A. McMaster University, Population Health Research Institute; Canadá.
Fil: Waskin, Hetty. Merck Sharp and Dohme Corporation; Estados Unidos.
Fil: Sosa-Estani, Sergio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Del Carmen Bangher, Maria. Instituto de Cardiología de Corrientes "Juana F. Cabral"; Argentina.
Fil: Cuneo, Carlos. Hospital San Bernardo. Prevención Cardiovascular; Salta, Argentina.
Fil: Milesi, Rodolfo. Centro de Diagnóstico y Rehabilitación, Santa Fe, Argentina.
Fil: Mallagray, Marcelo. Sanatorio Nuestra señora del Rosario. Centro de Investigaciones Médicas; Jujuy, Argentina.
Fil: Apt, Werner. Universidad de Chile. Facultad de Médicina. Instituto de Ciencias Biomédicas. Laboratorio Clínico Básico de Parasitología; Chile.
Fil: Beloscar, Juan. Hospital Provincial del Centenario; Rosario, Argentina.
Fil: Gascon, Joaquim. Hospital Clínico de Barcelona. Centro de Investigaciones Sanitarias Internacionales de Barcelona; España.
Fil: Molina, Israel. Universidad Autónoma de Barcelona. Hospital Universitario Vall d'Hebron. Departamento de Enfermedades Infecciosas. Programa del Instituto Catalán de Salud; España.
Fil: Echeverria, Luis E. Fundación Cardiovascular; Colombia.
Fil: Colombo, Hugo. Clínica Privada Colombo; Córdoba, Argentina.
Fil: Perez-Molina, Jose Antonio. Hospital Ramón Cajal. Centro Nacional de Referencias de Enfermedades Tropicales. Departamento de Enfermedades Infecciosas; Madrid, España.
Fil: Wyss, Fernando. Sociedad Centroamericana de Hipertensión Arterial y Prevención Cardiovascular; Guatemala.
Fil: Meeks, Brandi. McMaster University, Population Health Research Institute; Canadá.
Fil: Bonilla, Laura R. McMaster University, Population Health Research Institute; Canadá.
Fil: Gao, Peggy. McMaster University, Population Health Research Institute; Canadá.
Fil: Wei, Bo. Merck Sharp and Dohme Corporation; Estados Unidos.
Fil: McCarthy, Michael. Medimmune, Estados Unidos.
Fil: Yusuf, Salim. McMaster University, Population Health Research Institute; Canadá.
Background: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. Objectives: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. Methods: A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days. Results: Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole. Conclusions: Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480)
description Fil: Morillo, Carlos A. McMaster University, Population Health Research Institute; Canadá.
publishDate 2017
dc.date.none.fl_str_mv 2017-02-28
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sgc.anlis.gob.ar/handle/123456789/1448
10.1016/j.jacc.2016.12.023
url http://sgc.anlis.gob.ar/handle/123456789/1448
identifier_str_mv 10.1016/j.jacc.2016.12.023
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of the American College of Cardiology
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instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
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instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
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repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
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