{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:29:20Z","timestamp":1773296960711,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T00:00:00Z","timestamp":1502668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ibuprofen is an effective analgesic treatment with a ceiling effect at doses above 400\u00a0mg. This study compared the combination of ibuprofen 400\u00a0mg and caffeine 100\u00a0mg with ibuprofen 400\u00a0mg monotherapy, caffeine and placebo in the analgesic treatment of moderate to severe acute dental pain following third molar extraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>, active\u2010\/placebo\u2010controlled, double\u2010blind, single\u2010centre, two\u2010stage, parallel\u2010group study in adult patients with at least moderate baseline pain intensity. Primary endpoint was defined as the time\u2010weighted sum of pain relief and pain intensity difference over 8\u00a0h (<jats:styled-content style=\"fixed-case\">SPRID<\/jats:styled-content>0\u20138\u00a0h), secondary endpoints included duration of pain relief, time to meaningful pain relief and more.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>N<\/jats:italic>\u00a0=\u00a0748 patients were enrolled and <jats:italic>N<\/jats:italic>\u00a0=\u00a0562 treated. Mean baseline pain intensity was 7.7 on a 0\u201310 numerical rating scale. Analysis of <jats:styled-content style=\"fixed-case\">SPRID<\/jats:styled-content>0\u20138\u00a0h demonstrated superior analgesic effects for a single dose of ibuprofen\/caffeine versus ibuprofen, caffeine and placebo over 8\u00a0h, rescue medication in this stage was requested by more patients on ibuprofen (32.5%) than on ibuprofen\/caffeine (16.0%). Median time to meaningful pain relief was shorter for ibuprofen\/caffeine (1.13\u00a0h) compared with ibuprofen (1.78\u00a0h; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0001). More patients on ibuprofen\/caffeine than on ibuprofen reported meaningful pain relief. Adverse events were infrequent and mostly mild or moderate across treatment groups. Tolerability was rated as \u2018very good\u2019 or \u2018excellent\u2019 by most patients in both treatment groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated clinically relevant superiority of ibuprofen\/caffeine over monotherapy with ibuprofen in patients with acute dental pain. All treatments were well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This trial showed superior efficacy of 400\/100 mg ibuprofen\/caffeine, compared to 400\u00a0mg ibuprofen alone, for treating acute pain, reflecting that caffeine is an effective analgesic adjuvant. Data on efficacy of 400\u00a0mg ibuprofen combined with caffeine for the treatment of acute pain were not available yet.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1068","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T11:52:37Z","timestamp":1502711557000},"page":"28-38","source":"Crossref","is-referenced-by-count":33,"title":["Efficacy and safety of a fixed\u2010dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction"],"prefix":"10.1002","volume":"22","author":[{"given":"T.","family":"Weiser","sequence":"first","affiliation":[{"name":"Medical Affairs Consumer Health Care, Medical and Regulatory Affairs Germany Boehringer Ingelheim Pharma GmbH &amp; Co. KG Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Richter","sequence":"additional","affiliation":[{"name":"Corporate Division Medicine Global Department Biostatistics and Data Sciences Boehringer Ingelheim Pharma GmbH &amp; Co. KG Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Hegewisch","sequence":"additional","affiliation":[{"name":"Marketing Self\u2010Medication Global Department Consumer Health Care Division Medical and Regulatory Affairs Boehringer Ingelheim, Promeco S.A. de C.V Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.D.","family":"Muse","sequence":"additional","affiliation":[{"name":"Jean Brown Research Salt Lake City USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Lange","sequence":"additional","affiliation":[{"name":"Consumer Health Care Development Medical and Regulatory Affairs Boehringer Ingelheim Pharma GmbH &amp; Co. 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