{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:53:04Z","timestamp":1789228384891,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>STARDOM2 is a randomized, double\u2010blind, phase 3 trial evaluating the efficacy and safety of co\u2010crystal of tramadol\u2010celecoxib (CTC)\u2014a first\u2010in\u2010class analgesic co\u2010crystal comprising racemic tramadol hydrochloride and celecoxib in a supramolecular network that modifies their pharmacokinetic properties\u2014for the management of acute postoperative pain (NCT03062644; EudraCT:2016\u2013000593\u201038).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with moderate\u2010to\u2010severe pain following abdominal hysterectomy were randomized 2:2:2:2:2:1 to oral CTC 100\u2009mg (<jats:italic>rac<\/jats:italic>\u2010tramadol hydrochloride 44\u2009mg\/celecoxib 56\u2009mg) twice daily (BID); CTC 150\u2009mg (66\/84\u2009mg) BID; CTC 200\u2009mg (88\/112\u2009mg) BID; immediate\u2010release tramadol 100\u2009mg four times daily (QID); celecoxib 100\u2009mg BID; or placebo, for 5\u2009days. The primary endpoint was the sum of pain intensity differences over 0\u20134\u00a0h (SPID<jats:sub>0\u20134<\/jats:sub>). Key secondary endpoints were rescue medication use within 4\u00a0h, 50% response rate at 4\u00a0h, and safety\/tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 1355 patients enrolled, 1138 were randomized (full analysis set) and 1136 treated (safety analysis set). In the prespecified gatekeeping analysis of SPID<jats:sub>0\u20134<\/jats:sub>, CTC 200\u2009mg was not superior to tramadol but showed non\u2010inferior efficacy (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001) that was sustained throughout the 120\u2010h period, despite a 5\u2010day cumulative tramadol administration of 880\u2009mg with CTC 200\u2009mg BID versus 2000\u2009mg with tramadol 100\u2009mg QID. Treatment\u2010emergent adverse events (TEAEs) and severe TEAEs were less common with CTC 200\u2009mg versus tramadol. Treatment\u2010related TEAEs were 14.4% with CTC 200\u2009mg and 23.6% with tramadol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the study did not meet its primary endpoint, CTC 200\u2009mg showed a clinically relevant improvement in overall benefit\/risk profile versus tramadol alone, with considerably lower cumulative opioid exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In the randomized, double\u2010blind, phase 3 STARDOM2 trial\u2014in acute moderate\u2010to\u2010severe pain after abdominal hysterectomy\u2014the novel co\u2010crystal of tramadol\u2010celecoxib (CTC) 200\u2009mg BID was superior to placebo and non\u2010inferior to tramadol 100\u2009mg QID. Although superiority to tramadol was not reached, CTC 200\u2009mg BID exposed patients to lower cumulative opioid (tramadol) doses than tramadol (100\u2009mg QID) alone, with fewer treatment\u2010emergent adverse events. CTC 200\u2009mg thus has a clinically relevant improved benefit\/risk profile compared with tramadol alone.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.2021","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T05:08:50Z","timestamp":1660712930000},"page":"2083-2096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Efficacy and safety of co\u2010crystal of tramadol\u2010celecoxib (<scp>CTC<\/scp>) in acute moderate\u2010to\u2010severe pain after abdominal hysterectomy: A randomized, double\u2010blind, phase 3 trial (<scp>STARDOM2<\/scp>)"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-067X","authenticated-orcid":false,"given":"Richard","family":"Langford","sequence":"first","affiliation":[{"name":"The London Clinic  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3897-8966","authenticated-orcid":false,"given":"Adelaida","family":"Morte","sequence":"additional","affiliation":[{"name":"ESTEVE Pharmaceuticals S.A.  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