{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:00:56Z","timestamp":1783180856292,"version":"3.54.6"},"reference-count":82,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Demonstrating the efficacy of new treatments in any condition may be a challenging endeavor, and is particularly the case in sepsis. In the early 21st century, recombinant activated protein C showed a survival benefit in severe sepsis; however, subsequent studies could not replicate these results, leading to the discontinuation of this agent. Several potential reasons have been proposed for the unfavorable results of trials, including choosing an inappropriate outcome target. Concerning anticoagulant therapies, some studies have targeted sepsis with disseminated intravascular coagulation (DIC) and demonstrated clinical benefits, while other studies have focused on severe sepsis or septic shock independent of whether patients had DIC. The timing for treatment initiation, dosage, and duration of anticoagulant agents could be significant factors contributing to the limitations faced in these trials. Moreover, relying solely on 28-day mortality as the primary endpoint for sepsis trials may not be appropriate, as it can be influenced by various factors beyond anticoagulant therapies, and discernment in a shorter period might be more pertinent. Success in clinical trials is more likely if these issues are addressed and improvements are made. Recent clinical trials concentrating on anticoagulants are increasingly targeting sepsis or septic shock with coagulopathy, and adopting composite endpoints, including DIC resolution, is anticipated to overcome some of these challenges.<\/jats:p>","DOI":"10.1055\/a-2657-6380","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T23:13:47Z","timestamp":1753830827000},"page":"126-138","source":"Crossref","is-referenced-by-count":4,"title":["Evolution of Clinical Trials in Anticoagulation for Sepsis: Bridging Past to Future"],"prefix":"10.1055","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-4088","authenticated-orcid":false,"given":"Toshiaki","family":"Iba","sequence":"additional","affiliation":[{"name":"Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan"},{"name":"Faculty of Medical Science, Juntendo University, Urayasu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0895-6800","authenticated-orcid":false,"given":"Julie","family":"Helms","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit - NHC; INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg University (UNISTRA), Strasbourg University Hospital, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-2674","authenticated-orcid":false,"given":"Cheryl L.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-4747","authenticated-orcid":false,"given":"Ricard","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Intensive Care Department, Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4962","authenticated-orcid":false,"given":"Jerrold H.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00134-023-06980-6","article-title":"How to manage coagulopathies in critically ill 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