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

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  • dc.contributor.author Grillo, Sara
  • dc.contributor.author Gómez-Zorrilla, Silvia
  • dc.contributor.author Pujol, Miquel
  • dc.contributor.author SAFO study group and the Spanish Network for Research in Infectious Diseases (REIPI)
  • dc.date.accessioned 2022-05-24T06:32:48Z
  • dc.date.available 2022-05-24T06:32:48Z
  • dc.date.issued 2021
  • dc.description.abstract 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).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Grillo S, Cuervo G, Carratala J, San-Juan R, Aguado JM, Morata L, et al. 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. BMJ Open. 2021 Aug 5; 11(8): e051208. DOI: 10.1136/bmjopen-2021-051208
  • dc.identifier.doi http://dx.doi.org/10.1136/bmjopen-2021-051208
  • dc.identifier.issn 2044-6055
  • dc.identifier.uri http://hdl.handle.net/10230/53218
  • dc.language.iso eng
  • dc.publisher BMJ Publishing Group
  • dc.rights Copyright © Grillo, Sara; 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Clinical trials
  • dc.subject.keyword Infectious diseases
  • dc.subject.keyword Microbiology
  • dc.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
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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