{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:35:12Z","timestamp":1792805712463,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SepNet Critical Care Trials Group of the German Sepsis Foundation"},{"name":"Open Access Publication Fund of the University of Duisburg-Essen","id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Sepsis and septic shock are the most severe forms of infection. Due to the intensive cross-talk of the coagulation and immune system, coagulopathies regularly occur in sepsis. The International Society on Thrombosis and Hemostasis refers to these coagulation abnormalities as sepsis-induced coagulopathies (SICs). The presence of SICs can be assessed using the SIC score. In parallel, a score for \u201csepsis-associated coagulopathy\u201d (SAC) was introduced that, in contrast to the SIC score, allows coagulopathy to be classified according to its severity. In the past, multicenter, randomized controlled trials have repeatedly failed to prove the efficacy of specific therapeutic measures targeting SICs or SACs. This could potentially be explained by insufficient knowledge about the prevalence and incidence of SIC and the rate of spontaneous recovery. The Incidence of Sepsis-Induced Coagulopathy (INSIC) trial is intended to address this problem. Methods: The aim of the INSIC trial is to measure the incidence and prevalence of SIC\u2014in addition to the rate of spontaneous SIC recoveries\u2014during the first days of sepsis treatment to provide a solid base of data for future interventional trials. We aim to include all patients with sepsis treated in any one of 150 participating intensive care units in 100 hospitals located in Austria, Luxembourg, and Germany to determine the prevalence of SIC (on day 1 of the study period as well as on three selected days in the fourth quarter of each year from 2019 to 2024). SIC incidence will be assessed over a 14-day period starting on 10 March 2025. Secondary endpoints are 28-day survival and the occurrence of severe thromboembolic events and bleeding. In addition, each of the aforementioned outcome parameters will be assessed for correlation with the severity classification of the SAC score. Conclusions: The INSIC trial is the first study to determine the prevalence as well as the incidence of SIC, to prospectively examine the course of SIC longitudinally over a 14-day period, and to determine the rate of spontaneous recoveries within 72 h under standard treatment in a large cohort of patients. This information will provide a sound basis for future studies.<\/jats:p>","DOI":"10.3390\/jcm14124222","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:51:24Z","timestamp":1749808284000},"page":"4222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Incidence of Sepsis-Induced Coagulopathy (INSIC) Trial: Study Protocol of a Combined Retrospective and Prospective, Multicenter, International, Cross-Sectional, Longitudinal, and Epidemiological Observational Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2984-7718","authenticated-orcid":false,"given":"Thomas","family":"Schmoch","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45141 Essen, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, H\u00f4pitaux Robert Schuman\u2013H\u00f4pital Kirchberg, L-2540 Luxembourg City, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"M\u00f6hnle","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Anesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-038X","authenticated-orcid":false,"given":"Maximilian","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Gregorius","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45141 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-0339","authenticated-orcid":false,"given":"Sandra","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2837-8008","authenticated-orcid":false,"given":"Josef","family":"Briegel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Radke","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[{"name":"Center for Sepsis Control and Care, Jena University Hospital, 07747 Jena, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-7941","authenticated-orcid":false,"given":"Frank","family":"Bloos","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2666-8696","authenticated-orcid":false,"given":"Patrick","family":"Meybohm","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Bogatsch","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology (IMISE) and Clinical Trial Centre Leipzig, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45141 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1161\/CIRCRESAHA.116.306853","article-title":"Cross Talk Pathways Between Coagulation and Inflammation","volume":"118","year":"2016","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_3","unstructured":"Schmoch, T., Weigand, M., M\u00f6hnle, P., Briegel, J., and Brenner, T. (2025, June 08). Sepsis-Induzierte Koagulopathie: Zu h\u00e4ufig Missachtete Komplikation der Sepsis. INTENSIV-News [Internet]. Available online: https:\/\/medicom.cc\/de\/publikationen\/intensiv-news\/202306\/entries\/03-Sepsis-induzierte-Koagulopathie.php."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e017046","DOI":"10.1136\/bmjopen-2017-017046","article-title":"New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: A retrospective analysis of a nationwide survey","volume":"7","author":"Iba","year":"2017","journal-title":"BMJ Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1097\/CCM.0000000000002997","article-title":"Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality","volume":"46","author":"Lyons","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jamainternmed.2016.2514","article-title":"Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial","volume":"176","author":"Bloos","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1001\/jama.2016.14799","article-title":"Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial","volume":"316","author":"Keh","year":"2016","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13613-022-01093-7","article-title":"The prevalence of sepsis-induced coagulopathy in patients with sepsis\u2014A secondary analysis of two German multicenter randomized controlled trials","volume":"13","author":"Schmoch","year":"2023","journal-title":"Ann. Intensive Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/s12185-021-03152-4","article-title":"Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: Post hoc analysis of a nationwide multicenter observational study in Japan","volume":"114","author":"Tanaka","year":"2021","journal-title":"Int. J. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13613-020-00704-5","article-title":"Performances of disseminated intravascular coagulation scoring systems in septic shock patients","volume":"10","author":"Helms","year":"2020","journal-title":"Ann. Intensive Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1473-3099(12)70311-0","article-title":"Drotrecogin alfa (activated) in severe sepsis","volume":"13","author":"Marik","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1056\/NEJMoa1202290","article-title":"Drotrecogin Alfa (Activated) in Adults with Septic Shock","volume":"366","author":"Ranieri","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1001\/jama.2019.5358","article-title":"Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients with Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial","volume":"321","author":"Vincent","year":"2019","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13613-015-0058-8","article-title":"Timing and causes of death in septic shock","volume":"5","author":"Daviaud","year":"2015","journal-title":"Ann. Intensive Care"},{"key":"ref_16","unstructured":"Doyle, D.J., Goyal, A., and Garmon, E.H. (2022, June 01). American Society of Anesthesiologists Classification, StatPearls [Internet], Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK441940\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.7326\/0003-4819-152-1-201001050-00007","article-title":"Systematic review: Prediction of perioperative cardiac complications and mortality by the revised cardiac risk index","volume":"152","author":"Ford","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"SepNet Critical Care Trials Group (2016). Incidence of severe sepsis and septic shock in German intensive care units: The prospective, multicentre INSEP study. Intensive Care Med., 42, 1980\u20131989.","DOI":"10.1007\/s00134-016-4504-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jcrc.2018.11.009","article-title":"Epidemiology of disseminated intravascular coagulation in sepsis and validation of scoring systems","volume":"50","author":"Saito","year":"2019","journal-title":"J. Crit. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J. Biomed. Inform."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Harris, P.A., Taylor, R., Minor, B.L., Elliott, V., Fernandez, M., O\u2019Neal, L., McLeod, L., Delacqua, G., Delacqua, F., and Kirby, J. (2019). The REDCap consortium: Building an international community of software platform partners. J. Biomed. Inform., 95, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/31078660\/.","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"ref_22","unstructured":"Federal Law Gazette (2004). Ordinance on the implementation of Good Clinical Practice in the conduct of clinical trials on medicinal products for use in humans (GCP Ordinance-GCP-V). Fed. Law Gaz., 2004, 19."},{"key":"ref_23","unstructured":"(2021, February 06). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Official Web Site: ICH. Available online: https:\/\/www.ich.org\/."},{"key":"ref_24","unstructured":"The World Medical Association (WMA) (2019, August 15). Declaration of Helsinki\u2013Ethical Principles for Medical Research Involving Human Subjects. Available online: https:\/\/www.wma.net\/policies-post\/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects\/."},{"key":"ref_25","unstructured":"The European Parliament and of the Council (2025, June 08). General Data Protection Regulation (GDPR). Regulation (EU) 2016\/679 of the European Parliament and of the Council. 27 April 2016. Available online: https:\/\/gdpr-info.eu."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Peng, J.C., Nie, F., Li, Y.J., Xu, Q.Y., Xing, S.P., Li, W., and Gao, Y. (2022). Favorable Outcomes of Anticoagulation With Unfractioned Heparin in Sepsis-Induced Coagulopathy: A Retrospective Analysis of MIMIC-III Database. Front. Med., 8, Available online: https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.773339.","DOI":"10.3389\/fmed.2021.773339"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s13054-016-1415-1","article-title":"Benefit profile of anticoagulant therapy in sepsis: A nationwide multicentre registry in Japan","volume":"20","author":"Yamakawa","year":"2016","journal-title":"Crit. Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1097\/CCM.0000000000004426","article-title":"Effect of a Recombinant Human Soluble Thrombomodulin on Baseline Coagulation Biomarker Levels and Mortality Outcome in Patients with Sepsis-Associated Coagulopathy","volume":"48","author":"Levi","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1001\/jama.286.15.1869","article-title":"Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: A randomized controlled trial","volume":"286","author":"Warren","year":"2001","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1056\/NEJMoa050935","article-title":"Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death","volume":"353","author":"Abraham","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e950","DOI":"10.1002\/ams2.950","article-title":"Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression","volume":"11","author":"Tsuchida","year":"2024","journal-title":"Acute Med. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/MBC.0000000000000755","article-title":"Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: A retrospective study","volume":"29","author":"Ding","year":"2018","journal-title":"Blood Coagul Fibrinolysis"},{"key":"ref_33","first-page":"e1063","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Intensive Care Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:43Z","timestamp":1760032303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14124222"],"URL":"https:\/\/doi.org\/10.3390\/jcm14124222","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}