title: Idarucizumab for Dabigatran Reversal.
abstract: BACKGROUND
  Specific reversal agents for non-vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.
  
  
  METHODS
  We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required 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 determination at a central laboratory of the dilute thrombin time or ecarin clotting time. A key secondary end point was the restoration of hemostasis.
  
  
  RESULTS
  This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated.
  
  
  CONCLUSIONS
  Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.).
authors.affiliation: From Pennsylvania Hospital, Philadelphia (C.V.P.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (P.A.R., R.D., B.W.); McMaster University (J.E., J.I.W.) and Thrombosis and Atherosclerosis Research Institute (J.I.W.) - both in Hamilton, ON, Canada; Boehringer Ingelheim Pharma, Biberach (S.G., J.S.) and Ingelheim (J.K.), Klinikum Frankfurt Höchst, Frankfurt am Main, and Heidelberg University Hospital, Heidelberg (T.S.) - all in Germany; University of Leuven, Leuven, Belgium (P.V.); Northwestern University, Chicago (R.A.B.); Leiden University Medical Center, Leiden (M.V.H.), and University Medical Center Groningen, Groningen, (P.W.K.) - both in the Netherlands; Boston University School of Medicine, Boston (E.M.H.); Duke University Medical Center, Durham, NC (J.H.L.); Brown Medical School and Rhode Island Hospital, Providence, RI (F.W.S.); and Tuen Mun Hospital, Tuen Mun, NT, Hong Kong (C.-W.K.).
authors.forename: Charles V
authors.initials: CV
authors.lastname: Pollack
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Stephan
authors.initials: S
authors.lastname: Glund
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bernstein
authors.forename: Robert
authors.initials: R
authors.lastname: Dubiel
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuzer
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
authors.forename: Joachim
authors.initials: J
authors.lastname: Stangier
authors.forename: Thorsten
authors.initials: T
authors.lastname: Steiner
authors.forename: Bushi
authors.initials: B
authors.lastname: Wang
authors.forename: Chak-Wah
authors.initials: CW
authors.lastname: Kam
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000925:Anticoagulants / Q000009:adverse effects / Q000097:blood; D001562:Benzimidazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D000069604:Dabigatran; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013927:Thrombosis / Q000139:chemically induced / Q000453:epidemiology; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D001562:Benzimidazoles; D015091:beta-Alanine; C000594745:idarucizumab; D000069604:Dabigatran