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Efficacy and safety of a 4-factor prothrombin complex concentrate for rapid vitamin K antagonist reversal in Japanese patients presenting with major bleeding or requiring urgent surgical or invasive procedures: a prospective, open-label, single-arm phase 3b study

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Abstract

Rapid vitamin K antagonist (VKA) reversal is required in patients experiencing major bleeding or requiring urgent surgery. Four-factor prothrombin complex concentrate (4F-PCC; Beriplex®/Kcentra®) was shown in two large randomized controlled, international phase 3b trials to be an effective alternative to plasma for urgent VKA reversal. In the present prospective, open-label, single-arm phase 3b trial, we evaluate the efficacy and safety of 4F-PCC in Japanese patients. Eleven patients [international normalized ratio (INR) ≥2] requiring rapid VKA reversal owing to major bleeding (n = 6) or before urgent surgical/invasive procedures (n = 5) were administered 4F-PCC dosed based on INR and weight. INR reduction (≤1.3 0.5 h postinfusion; primary endpoint) was achieved in 81.8% of patients (major bleeding, 83.3%; surgical/invasive procedures, 80.0%). Effective hemostasis (main secondary endpoint) was met in 60.0% (major bleeding) and 100% (surgical/invasive procedure) of evaluable patients. Adverse events (AEs) and serious AEs were reported in 90.9 and 45.5% of patients, respectively. Two AEs were considered treatment-related; thromboembolic events rated mild and not clinically relevant by investigators. There were no deaths, fluid overload events, or viral transmission cases. Consistent with the previous results, 4F-PCC may be an effective and well-tolerated treatment for rapid VKA reversal in Japanese patients experiencing major bleeding or requiring urgent surgical/invasive procedures.

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Acknowledgements

This study was sponsored by CSL Behring. Medical writing assistance was provided by Leanne Regan of Fishawack Communications Ltd., funded by the sponsor.

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Authors and Affiliations

  1. Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Shigeki Kushimoto

  2. Kurashiki Central Hospital, Kurashiki, Japan

    Toshio Fukuoka

  3. Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan

    Akio Kimura

  4. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan

    Kazunori Toyoda

  5. CSL Behring, King of Prussia, PA, USA

    Andres Brainsky, Amy Harman & Thomas Chung

  6. National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan

    Masahiro Yasaka

Authors
  1. Shigeki Kushimoto
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  2. Toshio Fukuoka
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  3. Akio Kimura
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  4. Kazunori Toyoda
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  5. Andres Brainsky
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  6. Amy Harman
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  7. Thomas Chung
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  8. Masahiro Yasaka
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Corresponding author

Correspondence to Masahiro Yasaka.

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Conflict of interest

AB, AH, and TC are employees of CSL Behring. SK is on an advisory board for CSL Behring. TF, AK, KT, and MY declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Independent Ethics Committees of the participating centers and performed in accordance with local ethical and legal requirements. Written informed consent was obtained from all patients or their legally authorized representatives.

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Kushimoto, S., Fukuoka, T., Kimura, A. et al. Efficacy and safety of a 4-factor prothrombin complex concentrate for rapid vitamin K antagonist reversal in Japanese patients presenting with major bleeding or requiring urgent surgical or invasive procedures: a prospective, open-label, single-arm phase 3b study. Int J Hematol 106, 777–786 (2017). https://doi.org/10.1007/s12185-017-2311-4

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  • DOI: https://doi.org/10.1007/s12185-017-2311-4

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