title: A randomized, open-label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower-limb orthopedic surgery.
abstract: BACKGROUND
  Edoxaban is an oral, direct, factor Xa inhibitor approved in Japan for thromboembolic prophylaxis after lower-limb orthopedic surgery (LLOS), but contraindicated in patients with severe renal impairment (SRI; creatinine clearance [CLCR] ≥15 to <30 mL/min).
  
  
  METHODS
  This open-label study compared the safety of edoxaban 15 mg once daily in Japanese patients with SRI to that of edoxaban 30 mg in patients with mild renal impairment (MiRI; CLCR ≥50 to ≤80 mL/min; N = 30) undergoing LLOS. Patients with CLCR ≥20 to <30 mL/min were randomized to receive edoxaban 15 mg (N = 22) or subcutaneous fondaparinux 1.5 mg once daily (N = 21). All patients with CLCR ≥15 to <20 mL/min received edoxaban 15 mg (N = 7). Treatment was administered for 11 to 14 days.
  
  
  RESULTS
  Major or clinically relevant non-major bleeding occurred in 6.7%, 3.4%, and 5.0% of patients in the MiRI edoxaban 30-mg, SRI edoxaban 15-mg, and SRI fondaparinux groups, respectively; there were no major bleeding events. No thromboembolic events occurred. At all time points assessed, edoxaban plasma concentrations and changes in coagulation biomarkers were similar between the SRI and MiRI groups.
  
  
  CONCLUSIONS
  These results suggest edoxaban 15 mg once daily is well tolerated in Japanese patients with SRI undergoing LLOS.
  
  
  BACKGROUND
  Clinicaltrials.gov Identifier: NCT01857583.
authors: Department of Orthopaedic Surgery, Japan Community Healthcare Organization, Osaka Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003 Japan.
authors: Takeshi
authors: T
authors: Fuji
authors: Department of Orthopaedic Surgery, Takarazuka Daiichi Hospital, Takarazuka, Japan.
authors: Satoru
authors: S
authors: Fujita
authors: International University of Health and Welfare, Tokyo, Japan.
authors: Yohko
authors: Y
authors: Kawai
authors: Department of Orthopaedic Surgery, Kumamoto Chuo Hospital, Kumamoto, Japan.
authors: Yasuyuki
authors: Y
authors: Abe
authors: Clinical Planning Department, Daiichi Sankyo Co. Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710 Japan.
authors: Tetsuya
authors: T
authors: Kimura
authors: Clinical Execution Department, Daiichi Sankyo Co. Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710 Japan.
authors: Masayuki
authors: M
authors: Fukuzawa
authors: Clinical Data & Biostatistics Department, Daiichi Sankyo Co. Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710 Japan.
authors: Kenji
authors: K
authors: Abe
authors: Department of Orthopaedic Surgery, Mishuku Hospital, Tokyo, Japan.
authors: Shintaro
authors: S
authors: Tachibana
keywords: Edoxaban; Orthopedic surgery; Renal impairment; Thromboprophylaxis
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