{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T22:08:23Z","timestamp":1781215703938,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prolonged treatment with analgesic and sedative drugs in the pediatric intensive care unit (PICU) may lead to undesirable effects such as dependence and tolerance. Moreover, during analgosedation weaning, patients may develop clinical signs of withdrawal, known as withdrawal syndrome (WS). Some studies indicate that dexmedetomidine, a selective \u03b12-adrenoceptor agonist, may be useful to prevent WS, but no clear evidence supports these data. The aims of the present study are to evaluate the efficacy of dexmedetomidine in reducing the occurrence of WS during analgosedation weaning, and to clearly assess its safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We will perform an adaptive, multicenter, randomized, double-blind, placebo-controlled trial. Patients aged &lt;\u200918\u2009years receiving continuous intravenous analgosedation treatment for at least 5\u2009days and presenting with clinical conditions that allow analgosedation weaning will be randomly assigned to treatment A (dexmedetomidine) or treatment B (placebo). The treatment will be started 24\u2009h before the analgosedation weaning at 0.4 \u03bcg\/kg\/h, increased by 0.2 \u03bcg\/kg\/h per hour up to 0.8 \u03bcg\/kg\/h (neonate: 0.2 \u03bcg\/kg\/h, increased by 0.1 \u03bcg\/kg\/h per hour up to 0.4 \u03bcg\/kg\/h) and continued throughout the whole weaning time. The primary endpoint is the efficacy of the treatment, defined by the reduction in the WS rate among patients treated with dexmedetomidine compared with patients treated with placebo. Safety will be assessed by collecting any potentially related adverse event. The sample size assuring a power of 90% is 77 patients for each group (total\u00a0\n                      <jats:italic>N<\/jats:italic>\n                      =\u2009154 patients). The study was approved by the Ethics Committee of the University-Hospital S.Orsola-Malpighi of Bologna on 22 March 2017.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The present trial will allow us to clearly assess the efficacy of dexmedetomidine in reducing the occurrence of WS during weaning from analgosedation drugs. In addition, the study will provide a unique insight into the safety profile of dexmedetomidine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/eproofing.springer.com\/journals_v2\/mainpage.php?token=37RoNDHF542FiBZM_mgdQ4sqrSuqcVSIMOngdlht8GpR0mw3QTBde0d7aYx3RruJ\">NCT03645603<\/jats:ext-link>\n                      . Registered on 24 August 2018.\n                    <\/jats:p>\n                    <jats:p>EudraCT, 2015\u2013002114-80. Retrospectively registered on 2 January 2019.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-019-3793-6","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T09:07:10Z","timestamp":1576055230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Efficacy and safety of dexmedetomidine for prevention of withdrawal syndrome in the pediatric intensive care unit: protocol for an adaptive, multicenter, randomized, double-blind, placebo-controlled, non-profit clinical trial"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-3166","authenticated-orcid":false,"given":"Maria Cristina","family":"Mondardini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sperotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Daverio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Caramelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Gregori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Caligiuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vitale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Cecini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Piastra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Mancino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pettenazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Amigoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"3793_CR1","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1542\/peds.2009-0489","volume":"125","author":"KJ Anand","year":"2010","unstructured":"Anand KJ, Wilson DF, Berger J, Harrison R, Meert KL, Zimmerman J, et al. 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All centers approved the protocol. The study was also authorized by the Italian Medicines Agency National Authority. Written informed consent will be obtained from both parents of each involved child.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Orion Pharma assured the liability insurance of the study (total amount \u20ac10,758). The supporter had no role in the study design, decision to publish and preparation of the manuscript, and will have no access to or role in data collection and analysis. The authors have not received any personal funding or compensation for the research. Therefore, the authors did not have any personal interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"710"}}