A randomized, open-label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower-limb orthopedic surgery

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 [CL(CR)] ≥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; CL(CR) ≥50 to ≤80 mL/min; N = 30) undergoing LLOS. Patients with CL(CR) ≥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 CL(CR) ≥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. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01857583. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12959-014-0034-9) contains supplementary material, which is available to authorized users.