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

• Published in: BMJ open Vol. 11; no. 9; p. e049481
• Main Authors: Marín-Candón, Alicia, Rosso-Fernández, Clara M, Bustos de Godoy, Natalia, López-Cerero, Lorena, Gutiérrez-Gutiérrez, Belén, López-Cortés, Luis Eduardo, Barrera Pulido, Lydia, Borreguero Borreguero, Irene, León, María José, Merino, Vicente, Camean-Fernández, Manuel, Retamar, Pilar, Salamanca, Elena, Pascual, Alvaro, Rodriguez-Baño, Jesús
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 27-09-2021; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Antibiotics; Bacteremia - drug therapy; Bacteria; bacteriology; Cephalosporins - pharmacology; clinical pharmacology; Clinical Trials, Phase III as Topic; Drug dosages; Enterobacteriaceae - drug effects; Enzymes; Humans; Hypotheses; infection control; Infections; Infectious Diseases; Informed consent; Meropenem - therapeutic use; microbiology; Multicenter Studies as Topic; Pathogens; Patients; Penicillins - therapeutic use; Pharmacy; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Sepsis; Urogenital system; Spain; microbiology; clinical pharmacology; bacteriology; infection control; infectious diseases
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-049481

IntroductionAlternatives 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 analysisMulticentre, 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 disseminationThe 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 numberNCT04478721.