达比加群酯逆转剂依达鲁珠单抗：全队列分析。
Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.
机构信息
From Thomas Jefferson University, Philadelphia (C.V.P.); Boehringer Ingelheim, Ridgefield, CT (P.A.R., R.D., B.W.); Boehringer Ingelheim, Biberach (J.R., S.G., J.S.), Boehringer Ingelheim, Ingelheim am Rhein (J.K.), Klinikum Frankfurt Höchst, Frankfurt (T.S.), and Heidelberg University Hospital, Heidelberg (T.S.) - all in Germany; McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.E., J.I.W.); Feinberg School of Medicine, Northwestern University, Chicago (R.A.B.); Leiden University Medical Center, Leiden (M.V.H.), and Tergooi Hospital, Hilversum (P.W.K.) - both in the Netherlands; Boston University School of Medicine, Boston (E.M.H.); Tuen Mun Hospital, Hong Kong (C.-W.K.); Duke University School of Medicine, Durham, NC (J.H.L.); Middlemore Hospital (G.R.) and the University of Auckland (L.Y.) - both in Auckland, New Zealand; Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence (F.W.S.); and KU Leuven, Center for Molecular and Vascular Biology, Leuven, Belgium (P.V.).
出版信息
N Engl J Med. 2017 Aug 3;377(5):431-441. doi: 10.1056/NEJMoa1707278. Epub 2017 Jul 11.
BACKGROUND
Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.
METHODS
We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures.
RESULTS
A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals.
CONCLUSIONS
In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .).
背景
依达鲁单抗是一种单克隆抗体片段，被开发用于逆转达比加群的抗凝作用。
方法
我们进行了一项多中心、前瞻性、开放标签研究，以确定 5 克静脉注射依达鲁单抗是否能够逆转正在出血（A 组）或即将接受紧急手术（B 组）的患者的达比加群的抗凝作用。主要终点是依达鲁单抗给药后 4 小时内，基于稀释的凝血酶时间或蝰蛇凝血时间，达比加群抗凝作用的最大百分比逆转。次要终点包括止血和安全性措施的恢复。
结果
共有 503 名患者入组：A 组 301 例，B 组 202 例。基于稀释的凝血酶时间或蝰蛇凝血时间，达比加群的最大百分比逆转中位数为 100%（95%置信区间，100 至 100）。A 组 137 例（45.5%）患者出现胃肠道出血，98 例（32.6%）患者出现颅内出血；在可评估的患者中，出血停止的中位时间为 2.5 小时。B 组中，计划手术的中位启动时间为 1.6 小时；93.4%的患者围手术期止血正常，5.1%的患者轻度异常，1.5%的患者中度异常。90 天时，A 组有 6.3%的患者发生血栓事件，B 组有 7.4%的患者发生血栓事件，死亡率分别为 18.8%和 18.9%。没有严重的不良安全信号。
结论
在紧急情况下，依达鲁单抗迅速、持久和安全地逆转了达比加群的抗凝作用。（由勃林格殷格翰公司资助；RE-VERSE AD 临床试验.gov 编号，NCT02104947）。
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