{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T07:02:12Z","timestamp":1769583732033,"version":"3.49.0"},"reference-count":39,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008267","name":"Kong Christian den Tiendes Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008267","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fru Olga Bryde Nielsens Fond"},{"name":"A & J C Tvergaards Fond"},{"name":"Kaj og Hermilla Ostenfeld's Fond"},{"DOI":"10.13039\/501100006197","name":"A. P. M\u00f8ller Fonden til l\u00e6gevidenskabens fremme","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006197","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Danish Regions\u2019 Medicinal Grant","award":["EMN-2017-00901"],"award-info":[{"award-number":["EMN-2017-00901"]}]},{"DOI":"10.13039\/501100009418","name":"Nordsj\u00e6llands Hospital","doi-asserted-by":"publisher","award":["18526-e-20225"],"award-info":[{"award-number":["18526-e-20225"]}],"id":[{"id":"10.13039\/501100009418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,3,3]]},"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Current pharmacological treatment options for hyperemesis gravidarum have been introduced based on scarce evidence and are often not sufficiently effective. Several case reports suggest that mirtazapine, an antidepressant, may be an effective treatment for hyperemesis gravidarum, but so far there are no controlled trials investigating the potential effect of mirtazapine on hyperemesis gravidarum. The antiemetic ondansetron is currently widely used to treat hyperemesis gravidarum despite sparse evidence of effect in pregnant women. This study aims to investigate the effect of mirtazapine on hyperemesis gravidarum while also providing data on the effect of ondansetron.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This randomised double-blind placebo-controlled multicentre trial will be conducted in eight Danish hospitals. One hundred and eighty pregnant women referred to secondary care for hyperemesis gravidarum will be randomly allocated to 14-day treatment with either mirtazapine, ondansetron or placebo. Main inclusion criterion will be Pregnancy Unique Quantification of Emesis (PUQE-24) score \u226513\u2009or PUQE-24 score \u22657 if accompanied by weight loss &gt;5% of pre-pregnancy weight or hospitalisation. Participants are eligible regardless of whether other antiemetics, including ondansetron, have been tried. The coprimary outcomes are effects of mirtazapine and ondansetron, respectively, on PUQE-24 score tested hierarchically on day 2 and day 14. Secondary outcomes include, but are not limited to, differences between the three groups in number of daily vomiting episodes, dropout due to treatment failure, use of rescue medication, weight change and side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The trial has been approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. Results will be published in peer-reviewed journals and submitted to relevant conferences.<\/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\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03785691\">NCT03785691<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-034712","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T16:25:18Z","timestamp":1585067118000},"page":"e034712","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Validating the effect of Ondansetron and Mirtazapine In Treating hyperemesis gravidarum (VOMIT): protocol for a randomised placebo-controlled trial"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03785691","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"given":"Anne","family":"Ostenfeld","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hillerod, Denmark"},{"name":"Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonny Studsgaard","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina Bergmann","family":"Futtrup","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hillerod, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon Tr\u00e6rup","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas Kryger","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Research, Nordsjaellands Hospital, Hillerod, Denmark"},{"name":"Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne Brix","family":"Westergaard","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hillerod, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Henning","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4149-5663","authenticated-orcid":false,"given":"Ellen Christine Leth","family":"L\u00f8kkegaard","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hillerod, Denmark"},{"name":"Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"2025121402542761000_10.3.e034712.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(02)02024-0"},{"key":"2025121402542761000_10.3.e034712.2","first-page":"e171-83","article-title":"Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis","volume":"20","author":"Einarson","year":"2013","journal-title":"J Popul Ther Clin 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