{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:37:06Z","timestamp":1790087826395,"version":"4.0.1"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Millions of people take vitamin K antagonists (VKAs). Some people who need urgent surgical procedures require rapid VKA reversal to prevent excessive intraoperative bleeding.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the hemostatic noninferiority of an investigational 4-factor prothrombin complex concentrate (4F-PCC) to a control 4F-PCC for rapid VKA reversal before urgent surgery.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This phase 3, double-blind, noninferiority randomized clinical trial (LEX-209) was conducted in 24 hospitals in the US, Russia, Georgia, Belarus, Ukraine, and Romania from June 7, 2017, through November 8, 2021; the study was stopped in February 2022. Participants were adult patients taking VKA who had an international normalized ratio (INR) of 2 or higher and needed urgent surgery with a substantial bleeding risk (\u226550 mL). Patients were randomized 1:1 to a single infusion of either the investigational 4F-PCC or the control 4F-PCC. Data analysis followed intention-to-treat and per-protocol approaches.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Single intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU\/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measure<\/jats:title>\n The primary end point was hemostatic efficacy at surgery end. An independent adjudication board, blinded to the 4F-PCC treatment allocation, assessed hemostatic efficacy using an objective 4-point scale.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 208 patients (median [range] age, 67.5 [31-92] years; 118 males [56.7%]) received the investigational (n\u2009=\u2009105) or the control (n\u2009=\u2009103) 4F-PCC. The median (range) dose was 25 (16-50) IU\/kg in the investigational group and 25 (15-50) IU\/kg in the control group, with a median (range) infusion time of 12 (8-50) minutes and 13 (7-30) minutes and a median (range) time from infusion to surgery start of 1.42 (0.25-15.25) hours and 1.50 (0.42-18.50) hours, respectively. Baseline median (range) INR was 3.05 (1.97-21.10) in the investigational group and 3.00 (2.00-11.30) in the control group. In the intention-to-treat analysis, the investigational 4F-PCC was noninferior to the control 4F-PCC, resulting in effective hemostasis in 94.3% of patients vs 94.2% of patients (proportion difference, 0.001; 95% CI, \u22120.080 to 0.082;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), meeting the prespecified noninferiority margin of 0.15. An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, \u22120.056 to 0.181). Thrombotic events (2.9% vs 0%, respectively) and mortality (4.8% vs 1.0%, respectively) were no different than expected for 4F-PCC use. One patient in each treatment group discontinued due to adverse events (cardiac disorders unrelated to 4F-PCC).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar. These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT02740335<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.24758","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T11:51:54Z","timestamp":1722513114000},"page":"e2424758","source":"Crossref","is-referenced-by-count":9,"title":["Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates"],"prefix":"10.1001","volume":"7","author":[{"given":"Ravi","family":"Sarode","sequence":"first","affiliation":[{"name":"Division of Transfusion Medicine and Hemostasis, Department of Pathology, University of Texas Southwestern Medical Center, Dallas"},{"name":"Department of Internal Medicine (Hematology\/Oncology), University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua N.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Simonian","sequence":"additional","affiliation":[{"name":"Divison of Vascular Surgery, Heart and Vascular Hospital, Hackensack University Medical Center, Hackensack, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Hinterberger","sequence":"additional","affiliation":[{"name":"Octapharma Pharmazeutika Produktionsges m.b.H, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitrii","family":"Matveev","sequence":"additional","affiliation":[{"name":"Octapharma Pharmazeutika Produktionsges m.b.H, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gareis","sequence":"additional","affiliation":[{"name":"Octapharma Pharmazeutika Produktionsges m.b.H, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Truman J.","family":"Milling","sequence":"additional","affiliation":[{"name":"Tilman J. 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