{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:02:09Z","timestamp":1768482129610,"version":"3.49.0"},"reference-count":8,"publisher":"Georg Thieme Verlag KG","issue":"S 01","funder":[{"name":"GlaxoSmithKline"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Objective\u2003The aim of this study is to assess the efficacy and safety of retosiban in spontaneous preterm labor (sPTL).<\/jats:p><jats:p>\n          Study Design\u2003Two multicenter, randomized, and double-blind trials compared retosiban with placebo and retosiban with atosiban in women with a singleton pregnancy and intact membranes in sPTL at 24 to 336\/7 weeks' gestation. Coprimary endpoints in the placebo-controlled trial were time to delivery (TTD) or treatment failure (whichever occurred first) and neonatal composite morbidity and mortality. The primary endpoint of the atosiban comparator trial was TTD.<\/jats:p><jats:p>\n          Results\u2003The trials were terminated early because of slow recruitment. The placebo-controlled trial enrolled 23 participants (February 2016\u2013July 2017; 2.6% of target);the atosiban-comparator trial enrolled 97 (March 2015\u2013August 2017; 29% of target). Baseline participant characteristics were similar between treatments. In the placebo-controlled trial, mean gestational ages at randomization were 30.8 (retosiban, n\u2009=\u200910) and 30.5 weeks (placebo, n\u2009=\u200913), and mean times to delivery\/treatment failure were 18.9 days (retosiban) and 11.1 days (placebo). Two and four neonates in the retosiban and placebo groups, respectively, had \u22651 component of the neonatal composite endpoint. In the atosiban-comparator trial, mean gestational age at randomization was 31.5 weeks (for both retosiban, n\u2009=\u200947, and atosiban, n\u2009=\u200950), and adjusted mean TTDs were 32.51 days (retosiban) and 33.71 days (atosiban; p\u2009&gt;\u20090.05). Adverse events were no more common with retosiban than placebo or atosiban.<\/jats:p><jats:p>\n          Conclusion\u2003Despite considerable efforts to conduct two adequate and well-controlled studies in patients with sPTL, both studies were unable to recruit effectively and consequently terminated prematurely. Key factors negatively affecting participation were patient and physician resistance to use of a placebo comparator, lack of investigator consensus on diagnostic criteria and acceptance of protocol procedures, and ethics committee decisions. Meaningful cooperation between pharmaceutical companies, regulatory authorities, and the obstetric community is essential for future development of drugs to treat sPTL.<\/jats:p>","DOI":"10.1055\/s-0040-1710034","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T22:34:14Z","timestamp":1588890854000},"page":"e309-e317","source":"Crossref","is-referenced-by-count":8,"special_numbering":"S","title":["Randomized Trials of Retosiban Versus Placebo or Atosiban in Spontaneous Preterm Labor"],"prefix":"10.1055","volume":"38","author":[{"given":"George R.","family":"Saade","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Shennan","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, King's College London, St Thomas' Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen J.","family":"Beach","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Medicine, GSK, Research Triangle Park, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Hadar","sequence":"additional","affiliation":[{"name":"Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara V.","family":"Parilla","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Advocate Lutheran General Hospital, Park Ridge, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry","family":"Snidow","sequence":"additional","affiliation":[{"name":"Alternative Discovery and Development, GSK, Research Triangle Park, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcy","family":"Powell","sequence":"additional","affiliation":[{"name":"Central Safety Department, GSK, Research Triangle Park, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy H.","family":"Montague","sequence":"additional","affiliation":[{"name":"Clinical Statistics, Quantitative Sciences, GSK, Collegeville, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Statistics, Quantitative Sciences, GSK, Collegeville, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Maternal and Neonatal Health Unit, Alternative Discovery & Development, R&D, GSK, Research Triangle Park, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"McKain","sequence":"additional","affiliation":[{"name":"Pharmacovigilance, PPD, Wilmington, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Thornton","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"issue":"S 03","key":"ref1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1471-0528.2006.01133.x","article-title":"Regulatory and methodologic challenges to tocolytic development","volume":"113","author":"T M Goodwin","year":"2006","journal-title":"BJOG"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/bcp.12646","article-title":"Treatment of spontaneous preterm 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