{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T07:01:03Z","timestamp":1793948463693,"version":"4.8.0"},"reference-count":31,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"unspecified","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848041004"],"award-info":[{"award-number":["848041004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,10,17]]},"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Preterm birth complicates &gt;15\u2009million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48\u2009hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30\u201334 weeks), defined as uterine contractions with (1) a cervical length of &lt; 15 mm or (2) a cervical length of 15\u201330 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48\u2009hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 760 participants (380 per group) will detect a reduction in adverse neonatal outcome from 11.95% to 6% (alpha error 0.05, beta error 0.2). A cost-effectiveness analysis will be performed from a societal perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC\u2019s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>Nederlands Trial Register (Trial NL6469).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-029101","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T12:55:12Z","timestamp":1574772912000},"page":"e029101","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2156-8557","authenticated-orcid":false,"given":"Job","family":"Klumper","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Breebaart","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolien","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana A","family":"Naaktgeboren","sequence":"additional","affiliation":[{"name":"University Medical Centre Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"van der Post","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Bosmans","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"van Kaam","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Amsterdam UMC, Location AMC and VUmc, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewoud","family":"Schuit","sequence":"additional","affiliation":[{"name":"University Medical Centre Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands"},{"name":"Standford Prevention Research Center, Stanford University, Stanford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, School of Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelle","family":"Baalman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, National Maternity Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fionnuala","family":"McAuliffe","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, National Maternity Hospital, Dublin, Ireland"},{"name":"UCD Perinatal Research Centre, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8672-4365","authenticated-orcid":false,"given":"Martijn A","family":"Oudijk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"2025120518563358000_9.11.e029101.1","unstructured":"Howson CP , Kinney MV , Lawn JE , eds. 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