BMJ Open (Sep 2021)

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

DOI
https://doi.org/10.1136/bmjopen-2021-049481
Journal volume & issue
Vol. 11, no. 9

Abstract

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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.