Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Grillo, Sara; Cuervo Requena, Guillermo; Carratalà, Jordi; Sanjuan, Rafael; Aguado, José María; Morata, Laura; Gómez-Zorrilla Martín, Silvia; López-Contreras, Joaquín; Gasch, Oriol; Gomila Grange, Aina; Iftimie, Simona; Garcia Pardo, Graciano; Calbo, Esther; Boix Palop, Lucía; Oriol, Isabel; Jover-Sáenz, Alfredo; López-Cortés, Luis Eduardo; Euba, Gorane; Aguirregabiria, Malen; Garcia-Pais, Maria Jose; Gioia, Francesca; Paño Pardo, José Ramón; Pedro-Botet Montoya, Ma Luisa; Benítez, Rosa M.; Pérez-Rodríguez, Maria Teresa; Meije, Yolanda; Loeches-Yagüe, Maria Belén; Horna, Gertrudis; Berbel, Dàmaris; Domínguez, María Ángeles; Padullés Zamora, Ariadna; Cobo Sacristán, Sara; Hereu, Pilar; Videla, Sebastià; Tebé, Cristian; Pallarès, Natàlia; Miró Meda, José M. (José María), 1956-; Pujol Rojo, Miquel; SAFO study group; Spanish Network for Research in Infectious Diseases (REIPI).

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam mo...

Descripción completa

Detalles Bibliográficos
Autores:	Grillo, Sara, Cuervo Requena, Guillermo, Carratalà, Jordi, Sanjuan, Rafael, Aguado, José María, Morata, Laura, Gómez-Zorrilla Martín, Silvia, López-Contreras, Joaquín, Gasch, Oriol, Gomila Grange, Aina, Iftimie, Simona, Garcia Pardo, Graciano, Calbo, Esther, Boix Palop, Lucía, Oriol, Isabel, Jover-Sáenz, Alfredo, López-Cortés, Luis Eduardo, Euba, Gorane, Aguirregabiria, Malen, Garcia-Pais, Maria Jose, Gioia, Francesca, Paño Pardo, José Ramón, Pedro-Botet Montoya, Ma Luisa, Benítez, Rosa M., Pérez-Rodríguez, Maria Teresa, Meije, Yolanda, Loeches-Yagüe, Maria Belén, Horna, Gertrudis, Berbel, Dàmaris, Domínguez, María Ángeles, Padullés Zamora, Ariadna, Cobo Sacristán, Sara, Hereu, Pilar, Videla, Sebastià, Tebé, Cristian, Pallarès, Natàlia, Miró Meda, José M. (José María), 1956-, Pujol Rojo, Miquel, SAFO study group, Spanish Network for Research in Infectious Diseases (REIPI).
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2021
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/198352
Acceso en línea:	https://hdl.handle.net/2445/198352
Access Level:	acceso abierto
Palabra clave:	Malalties infeccioses Microbiologia Assaigs clínics Communicable diseases Microbiology Clinical trials

id	ES_b43519c73d03620faaf002debfadcdcd
oai_identifier_str	oai:recercat.cat:2445/198352
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
title	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
spellingShingle	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial Grillo, Sara Malalties infeccioses Microbiologia Assaigs clínics Communicable diseases Microbiology Clinical trials
title_short	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
title_full	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
title_fullStr	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
title_full_unstemmed	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
title_sort	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
dc.creator.none.fl_str_mv	Grillo, Sara Cuervo Requena, Guillermo Carratalà, Jordi Sanjuan, Rafael Aguado, José María Morata, Laura Gómez-Zorrilla Martín, Silvia López-Contreras, Joaquín Gasch, Oriol Gomila Grange, Aina Iftimie, Simona Garcia Pardo, Graciano Calbo, Esther Boix Palop, Lucía Oriol, Isabel Jover-Sáenz, Alfredo López-Cortés, Luis Eduardo Euba, Gorane Aguirregabiria, Malen Garcia-Pais, Maria Jose Gioia, Francesca Paño Pardo, José Ramón Pedro-Botet Montoya, Ma Luisa Benítez, Rosa M. Pérez-Rodríguez, Maria Teresa Meije, Yolanda Loeches-Yagüe, Maria Belén Horna, Gertrudis Berbel, Dàmaris Domínguez, María Ángeles Padullés Zamora, Ariadna Cobo Sacristán, Sara Hereu, Pilar Videla, Sebastià Tebé, Cristian Pallarès, Natàlia Miró Meda, José M. (José María), 1956- Pujol Rojo, Miquel SAFO study group Spanish Network for Research in Infectious Diseases (REIPI).
author	Grillo, Sara
author_facet	Grillo, Sara Cuervo Requena, Guillermo Carratalà, Jordi Sanjuan, Rafael Aguado, José María Morata, Laura Gómez-Zorrilla Martín, Silvia López-Contreras, Joaquín Gasch, Oriol Gomila Grange, Aina Iftimie, Simona Garcia Pardo, Graciano Calbo, Esther Boix Palop, Lucía Oriol, Isabel Jover-Sáenz, Alfredo López-Cortés, Luis Eduardo Euba, Gorane Aguirregabiria, Malen Garcia-Pais, Maria Jose Gioia, Francesca Paño Pardo, José Ramón Pedro-Botet Montoya, Ma Luisa Benítez, Rosa M. Pérez-Rodríguez, Maria Teresa Meije, Yolanda Loeches-Yagüe, Maria Belén Horna, Gertrudis Berbel, Dàmaris Domínguez, María Ángeles Padullés Zamora, Ariadna Cobo Sacristán, Sara Hereu, Pilar Videla, Sebastià Tebé, Cristian Pallarès, Natàlia Miró Meda, José M. (José María), 1956- Pujol Rojo, Miquel SAFO study group Spanish Network for Research in Infectious Diseases (REIPI).
author_role	author
author2	Cuervo Requena, Guillermo Carratalà, Jordi Sanjuan, Rafael Aguado, José María Morata, Laura Gómez-Zorrilla Martín, Silvia López-Contreras, Joaquín Gasch, Oriol Gomila Grange, Aina Iftimie, Simona Garcia Pardo, Graciano Calbo, Esther Boix Palop, Lucía Oriol, Isabel Jover-Sáenz, Alfredo López-Cortés, Luis Eduardo Euba, Gorane Aguirregabiria, Malen Garcia-Pais, Maria Jose Gioia, Francesca Paño Pardo, José Ramón Pedro-Botet Montoya, Ma Luisa Benítez, Rosa M. Pérez-Rodríguez, Maria Teresa Meije, Yolanda Loeches-Yagüe, Maria Belén Horna, Gertrudis Berbel, Dàmaris Domínguez, María Ángeles Padullés Zamora, Ariadna Cobo Sacristán, Sara Hereu, Pilar Videla, Sebastià Tebé, Cristian Pallarès, Natàlia Miró Meda, José M. (José María), 1956- Pujol Rojo, Miquel SAFO study group Spanish Network for Research in Infectious Diseases (REIPI).
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 author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Malalties infeccioses Microbiologia Assaigs clínics Communicable diseases Microbiology Clinical trials
topic	Malalties infeccioses Microbiologia Assaigs clínics Communicable diseases Microbiology Clinical trials
description	Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.
publishDate	2021
dc.date.none.fl_str_mv	2021 2023 2023 2023
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/198352
url	https://hdl.handle.net/2445/198352
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1136/bmjopen-2021-051208 BMJ Open, 2021, vol. 11, num. 8, p. e051208 https://doi.org/10.1136/bmjopen-2021-051208
dc.rights.none.fl_str_mv	cc-by (c) Grillo, Sara et al., 2021 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Grillo, Sara et al., 2021 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	20 p. application/pdf
dc.publisher.none.fl_str_mv	BMJ Publishing Group
publisher.none.fl_str_mv	BMJ Publishing Group
dc.source.none.fl_str_mv	Articles publicats en revistes (Patologia i Terapèutica Experimental) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869417241559171072
spelling	Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trialGrillo, SaraCuervo Requena, GuillermoCarratalà, JordiSanjuan, RafaelAguado, José MaríaMorata, LauraGómez-Zorrilla Martín, SilviaLópez-Contreras, JoaquínGasch, OriolGomila Grange, AinaIftimie, SimonaGarcia Pardo, GracianoCalbo, EstherBoix Palop, LucíaOriol, IsabelJover-Sáenz, AlfredoLópez-Cortés, Luis EduardoEuba, GoraneAguirregabiria, MalenGarcia-Pais, Maria JoseGioia, FrancescaPaño Pardo, José RamónPedro-Botet Montoya, Ma LuisaBenítez, Rosa M.Pérez-Rodríguez, Maria TeresaMeije, YolandaLoeches-Yagüe, Maria BelénHorna, GertrudisBerbel, DàmarisDomínguez, María ÁngelesPadullés Zamora, AriadnaCobo Sacristán, SaraHereu, PilarVidela, SebastiàTebé, CristianPallarès, NatàliaMiró Meda, José M. (José María), 1956-Pujol Rojo, MiquelSAFO study groupSpanish Network for Research in Infectious Diseases (REIPI).Malalties infecciosesMicrobiologiaAssaigs clínicsCommunicable diseasesMicrobiologyClinical trialsIntroduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.BMJ Publishing Group2023202320212023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 p.application/pdfhttps://hdl.handle.net/2445/198352Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1136/bmjopen-2021-051208BMJ Open, 2021, vol. 11, num. 8, p. e051208https://doi.org/10.1136/bmjopen-2021-051208cc-by (c) Grillo, Sara et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1983522026-05-29T05:05:01Z
score	15,812455

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Similares en LA Referencia