Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/54910 |
Resumo: | Programa de Excelência em Pesquisa Clínica da Fiocruz. Conselho Nacional de Pesquisa (CNPq). |
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Macedo, Carolina TLarocca, Ticiana FRabelo, Márcia NoyaAras Jr, RoqueMacedo, Cristiano R. BMoreira, Moisés ICaldas, Alessandra CTorreão, Jorge AMonsão, Victor M. ASouza, Clarissa L. MVasconcelos, Juliana FBezerra, Milena RPetri, Daniela PSouza, Bruno S. FPacheco, Antônio G. FDaher, AndréSantos, Ricardo Ribeiro dosSoares, Milena B. P2022-09-28T12:48:04Z2022-09-28T12:48:04Z2022MACEDO, Carolina T. et al. Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial. Frontiers in Cardiovascular Medicine, v. 9, p. 1-10, 2022.2297-055Xhttps://www.arca.fiocruz.br/handle/icict/5491010.3389/fcvm.2022.864837Programa de Excelência em Pesquisa Clínica da Fiocruz. Conselho Nacional de Pesquisa (CNPq).Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Senai de Inovação em Sistemas Avançados de Saúde. SENAI CIMATEC. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Salvador, BA, Brasil.Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Salvador, BA, Brasil.Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil.Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil.Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil.Hospital Geral Roberto Santos. Salvador, BA, Brasil.Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Instituto Senai de Inovação em Sistemas Avançados de Saúde. SENAI CIMATEC. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / D’Or Instituto de Pesquisa e Educação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Vice-Presidência de Laboratórios de Pesquisa e Referência. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Senai de Inovação em Sistemas Avançados de Saúde. SENAI CIMATEC. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Senai de Inovação em Sistemas Avançados de Saúde. SENAI CIMATEC. Salvador, BA, Brasil.Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6–12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60–0.97) vs. 66% (95% CI 0.40–0.86), p = 0.47, at 6 months and 68% (95% CI 0.43–0.87) vs. 72% (95% CI 0.46–0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients.engFrontiers MediaChagas CardiomyopathyTerapia G-CSFEstudo de segurançaAnálise funcional cardíacaClasse funcional NYHACardiomiopatia chagásicaG-CSF therapySafety studyCardiac functional analysisNYHA functional classChagas cardiomyopathyCardiomiopatia ChagásicaEfficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trialinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/54910/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMacedo, Carolina Thé - Efficacy and safety of granulocyt colony stimulat.pdfMacedo, Carolina Thé - Efficacy and safety of granulocyt colony stimulat.pdfapplication/pdf1663007https://www.arca.fiocruz.br/bitstream/icict/54910/2/Macedo%2c%20Carolina%20Th%c3%a9%20-%20Efficacy%20and%20safety%20of%20granulocyt%20colony%20stimulat.pdfb6138c5484bd3fadc577d84b33416761MD52icict/549102023-03-15 14:32:53.283oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:32:53Repositório Institucional da FIOCRUZ (ARCA) - 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| dc.title.en_US.fl_str_mv |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| title |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| spellingShingle |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial Macedo, Carolina T Chagas Cardiomyopathy Terapia G-CSF Estudo de segurança Análise funcional cardíaca Classe funcional NYHA Cardiomiopatia chagásica G-CSF therapy Safety study Cardiac functional analysis NYHA functional class Chagas cardiomyopathy Cardiomiopatia Chagásica |
| title_short |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| title_full |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| title_fullStr |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| title_full_unstemmed |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| title_sort |
Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial |
| author |
Macedo, Carolina T |
| author_facet |
Macedo, Carolina T Larocca, Ticiana F Rabelo, Márcia Noya Aras Jr, Roque Macedo, Cristiano R. B Moreira, Moisés I Caldas, Alessandra C Torreão, Jorge A Monsão, Victor M. A Souza, Clarissa L. M Vasconcelos, Juliana F Bezerra, Milena R Petri, Daniela P Souza, Bruno S. F Pacheco, Antônio G. F Daher, André Santos, Ricardo Ribeiro dos Soares, Milena B. P |
| author_role |
author |
| author2 |
Larocca, Ticiana F Rabelo, Márcia Noya Aras Jr, Roque Macedo, Cristiano R. B Moreira, Moisés I Caldas, Alessandra C Torreão, Jorge A Monsão, Victor M. A Souza, Clarissa L. M Vasconcelos, Juliana F Bezerra, Milena R Petri, Daniela P Souza, Bruno S. F Pacheco, Antônio G. F Daher, André Santos, Ricardo Ribeiro dos Soares, Milena B. P |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Macedo, Carolina T Larocca, Ticiana F Rabelo, Márcia Noya Aras Jr, Roque Macedo, Cristiano R. B Moreira, Moisés I Caldas, Alessandra C Torreão, Jorge A Monsão, Victor M. A Souza, Clarissa L. M Vasconcelos, Juliana F Bezerra, Milena R Petri, Daniela P Souza, Bruno S. F Pacheco, Antônio G. F Daher, André Santos, Ricardo Ribeiro dos Soares, Milena B. P |
| dc.subject.mesh.en_US.fl_str_mv |
Chagas Cardiomyopathy |
| topic |
Chagas Cardiomyopathy Terapia G-CSF Estudo de segurança Análise funcional cardíaca Classe funcional NYHA Cardiomiopatia chagásica G-CSF therapy Safety study Cardiac functional analysis NYHA functional class Chagas cardiomyopathy Cardiomiopatia Chagásica |
| dc.subject.other.en_US.fl_str_mv |
Terapia G-CSF Estudo de segurança Análise funcional cardíaca Classe funcional NYHA Cardiomiopatia chagásica |
| dc.subject.en.en_US.fl_str_mv |
G-CSF therapy Safety study Cardiac functional analysis NYHA functional class Chagas cardiomyopathy |
| dc.subject.decs.en_US.fl_str_mv |
Cardiomiopatia Chagásica |
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Programa de Excelência em Pesquisa Clínica da Fiocruz. Conselho Nacional de Pesquisa (CNPq). |
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2022 |
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2022-09-28T12:48:04Z |
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2022-09-28T12:48:04Z |
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2022 |
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MACEDO, Carolina T. et al. Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial. Frontiers in Cardiovascular Medicine, v. 9, p. 1-10, 2022. |
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https://www.arca.fiocruz.br/handle/icict/54910 |
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2297-055X |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fcvm.2022.864837 |
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MACEDO, Carolina T. et al. Efficacy and safety of granulocyte-colony stimulating factor therapy in chagas cardiomyopathy: a phase II double-blind, randomized, placebo-controlled clinical trial. Frontiers in Cardiovascular Medicine, v. 9, p. 1-10, 2022. 2297-055X 10.3389/fcvm.2022.864837 |
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