Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor
prothrombin complex concentrate.
Author(s): Zahir H(1), Brown KS(2), Vandell AG(2), Desai M(2), Maa JF(2), Dishy V(2), Lomeli
B(2), Feussner A(2), Feng W(2), He L(2), Grosso MA(2), Lanz HJ(2), Antman EM(2).
Affiliation(s): Author information:
(1)From Daiichi Sankyo Pharma Development, Edison, NJ (H.Z., K.S.B., A.G.V.,
M.D., V.D., W.F., L.H., M.A.G., H.J.L.); Daiichi Sankyo Inc., Parsippany, NJ
(J.-F.M.); Quintiles Inc., Overland, KS (B.L.); CSL Behring GmbH, Marburg,
Germany (A.F.); and Brigham and Women's Hospital, Harvard Medical School, Boston,
MA (E.M.A.). hzahir@dsi.com. (2)From Daiichi Sankyo Pharma Development, Edison,
NJ (H.Z., K.S.B., A.G.V., M.D., V.D., W.F., L.H., M.A.G., H.J.L.); Daiichi Sankyo
Inc., Parsippany, NJ (J.-F.M.); Quintiles Inc., Overland, KS (B.L.); CSL Behring
GmbH, Marburg, Germany (A.F.); and Brigham and Women's Hospital, Harvard Medical
School, Boston, MA (E.M.A.).
Publication date & source: 2015, Circulation. , 131(1):82-90
BACKGROUND: The oral factor Xa inhibitor edoxaban has demonstrated safety and
efficacy in stroke prevention in patients with atrial fibrillation and in the
treatment and secondary prevention of venous thromboembolism. This study
investigated the reversal of edoxaban's effects on bleeding measures and
biomarkers by using a 4-factor prothrombin complex concentrate (4F-PCC).
METHODS AND RESULTS: This was a phase 1 study conducted at a single site. This
was a double-blind, randomized, placebo-controlled, 2-way crossover study to
determine the reversal effect of descending doses of 4F-PCC on bleeding duration
and bleeding volume following edoxaban treatment. A total of 110 subjects (17 in
part 1, 93 in part 2) were treated. Intravenous administration of 4F-PCC 50, 25,
or 10 IU/kg following administration of edoxaban (60 mg) dose-dependently
reversed edoxaban's effects on bleeding duration and endogenous thrombin
potential, with complete reversal at 50 IU/kg. Effects on prothrombin time were
partially reversed at 50 IU/kg. A similar trend was seen for bleeding volume.
CONCLUSIONS: The 4F-PCC dose-dependently reversed the effects of edoxaban (60
mg), with complete reversal of bleeding duration and endogenous thrombin
potential and partial reversal of prothrombin time following 50 IU/kg. Edoxaban
alone and in combination with 4F-PCC was safe and well tolerated in these healthy
subjects. A dose of 50 IU/kg 4F-PCC may be suitable for reversing edoxaban
anticoagulation.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
identifier: NCT02047565.
Erratum in
Circulation. 2015 Jan 6;131(1):e10.
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