Takeshi Fuji1, Ching-Jen Wang2, Satoru Fujita3, Yohko Kawai4, Mashio Nakamura5, Tetsuya Kimura6, Kei Ibusuki7, Hitoshi Ushida8, Kenji Abe9, Shintaro Tachibana10. 1. The Department of Orthopedic Surgery, Japan Community Healthcare Organization, Osaka Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003, Japan. Electronic address: fuji-th@umin.ac.jp. 2. Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan. Electronic address: w281211@adm.cgmh.org.tw. 3. Department of Orthopedic Surgery, Takarazuka Daiichi Hospital, 19-5 Kogetsu-cho, Takarazuka, 665-0832, Japan. Electronic address: fujita@takarazuka-daiichi-hp.or.jp. 4. International University of Health and Welfare, 8-10-16 Akasaka, Minato-ku, Tokyo 107-0002 Japan. Electronic address: yohko@iuhw.ac.jp. 5. Department of Clinical Cardiovascular Research, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan. Electronic address: mashio@clin.medic.mie-u.ac.jp. 6. Clinical Planning Department, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: kimura.tetsuya.d2@daiichisankyo.co.jp. 7. Clinical Planning Department, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: ibusuki.kei.tx@daiichisankyo.co.jp. 8. Asia Development Department, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: ushida.hitoshi.e8@rdn.daiichisankyo.co.jp. 9. Clinical Data & Biostatistics Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: abe.kenji.v7@daiichisankyo.co.jp. 10. Department of Orthopedic Surgery, Mishuku Hospital, 5-33-12 Shimomeguro, Meguro-ku, Tokyo, 153-0051, Japan. Electronic address: s-tachi@mishuku.gr.jp.
Abstract
INTRODUCTION: This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with enoxaparin sodium (enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions. RESULTS: Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and enoxaparin groups, respectively (relative risk reduction=46.8%), indicating non-inferiority (P <0.001) and superiority (P=0.010) of edoxaban versus enoxaparin. In the edoxaban and enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients (P=0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients (P=0.129), respectively. CONCLUSIONS:Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.
RCT Entities:
INTRODUCTION: This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with enoxaparin sodium (enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions. RESULTS: Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and enoxaparin groups, respectively (relative risk reduction=46.8%), indicating non-inferiority (P <0.001) and superiority (P=0.010) of edoxaban versus enoxaparin. In the edoxaban and enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients (P=0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients (P=0.129), respectively. CONCLUSIONS:Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.
Authors: Abiram Bala; James I Huddleston; Stuart B Goodman; William J Maloney; Derek F Amanatullah Journal: Clin Orthop Relat Res Date: 2017-05-31 Impact factor: 4.176
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Authors: David R Anderson; Gian Paolo Morgano; Carole Bennett; Francesco Dentali; Charles W Francis; David A Garcia; Susan R Kahn; Maryam Rahman; Anita Rajasekhar; Frederick B Rogers; Maureen A Smythe; Kari A O Tikkinen; Adolph J Yates; Tejan Baldeh; Sara Balduzzi; Jan L Brożek; Itziar Etxeandia- Ikobaltzeta; Herman Johal; Ignacio Neumann; Wojtek Wiercioch; Juan José Yepes-Nuñez; Holger J Schünemann; Philipp Dahm Journal: Blood Adv Date: 2019-12-10
Authors: Dimitrios V Papadopoulos; Ioannis Kostas-Agnantis; Ioannis Gkiatas; Andreas G Tsantes; Panagiota Ziara; Anastasios V Korompilias Journal: Eur J Orthop Surg Traumatol Date: 2017-03-17