{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T10:54:45Z","timestamp":1783680885094,"version":"3.55.0"},"reference-count":20,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"unspecified","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI19\/00093"],"award-info":[{"award-number":["ICI19\/00093"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"REIPI","award":["RD16\/0016\/000,1 0002, 0004, 0008, 0009, 0010, 0011"],"award-info":[{"award-number":["RD16\/0016\/000,1 0002, 0004, 0008, 0009, 0010, 0011"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,9,6]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant <jats:italic>Enterobacterales<\/jats:italic> (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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>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\u201310 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04478721\">NCT04478721<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-049481","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T13:27:55Z","timestamp":1632749275000},"page":"e049481","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant <i>Enterobacterales<\/i> (ASTART\u00c9): protocol for a randomised, pragmatic trial"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04478721","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Alicia","family":"Mar\u00edn-Cand\u00f3n","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n Cl\u00ednica y Ensayos Cl\u00ednicos (CTU), Hospital Universitario Virgen del Rocio, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara M","family":"Rosso-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Cl\u00ednica y Ensayos Cl\u00ednicos (CTU), Hospital Universitario Virgen del Rocio, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Bustos de Godoy","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena, Sevilla, Spain"},{"name":"Departamentos de Medicina y Microbiolog\u00eda, Universidad 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