Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial

Alicia Marín-Candón, Clara M Rosso-Fernández, Natalia Bustos de Godoy, Lorena López-Cerero, Belén Gutiérrez-Gutiérrez, Luis Eduardo López-Cortés, Lydia Barrera Pulido, Irene Borreguero Borreguero, María José León, Vicente Merino, Manuel Camean-Fernández, Pilar Retamar, Elena Salamanca, Alvaro Pascual, Jesús Rodriguez-Baño, ASTARTÉ Study Group, Alicia Marín-Candón, Clara M Rosso-Fernández, Natalia Bustos de Godoy, Lorena López-Cerero, Belén Gutiérrez-Gutiérrez, Luis Eduardo López-Cortés, Lydia Barrera Pulido, Irene Borreguero Borreguero, María José León, Vicente Merino, Manuel Camean-Fernández, Pilar Retamar, Elena Salamanca, Alvaro Pascual, Jesús Rodriguez-Baño, ASTARTÉ Study Group

Abstract

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.

Keywords: bacteriology; clinical pharmacology; infection control; infectious diseases; microbiology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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