Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial
Jesús Rodríguez-Baño,
Clara M Rosso-Fernández,
Pilar Retamar,
Belén Gutiérrez-Gutiérrez,
Alvaro Pascual,
Elena Salamanca,
Vicente Merino,
Luis Eduardo López-Cortés,
Alicia Marín-Candón,
Natalia Bustos de Godoy,
Lorena López-Cerero,
Lydia Barrera Pulido,
Irene Borreguero Borreguero,
María José León,
Manuel Camean-Fernández
Affiliations
Jesús Rodríguez-Baño
Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)/CSIC; CIBERINFEC, Sevilla, Spain
Clara M Rosso-Fernández
Unidad de Investigación Clínica y Ensayos Clínicos (CTU-UICEC-HUVR-HUVM), Hospital Universitario Virgen del Rocío, Sevilla, Spain
Pilar Retamar
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Belén Gutiérrez-Gutiérrez
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Alvaro Pascual
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Elena Salamanca
Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Vicente Merino
Unidad Clínica de Farmacia, Hospital Universitario Virgen Macarena, Sevilla, Spain
Luis Eduardo López-Cortés
Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Alicia Marín-Candón
Clinical Pharmacology Department, La Paz University Hospital, IdiPAZ, Madrid, Spain
Natalia Bustos de Godoy
Departamentos de Medicina y Microbiología, Universidad de Sevilla, Sevilla, Spain
Lorena López-Cerero
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Lydia Barrera Pulido
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
Irene Borreguero Borreguero
Unidad de Investigación Clínica y Ensayos Clínicos (CTU-UICEC-HUVR-HUVM), Hospital Universitario Virgen del Rocío, Sevilla, Spain
María José León
Unidad de Investigación Clínica y Ensayos Clínicos (CTU), Hospital Universitario Virgen del Rocio, Sevilla, Spain
Manuel Camean-Fernández
Unidad Clínica de Farmacia, Hospital Universitario Virgen Macarena, Sevilla, Spain
Introduction Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E.Methods and analysis Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7–10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population.Ethics and dissemination The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals.Trial registration number NCT04478721.