Ha Chul-Won, Park Yong-Beom, Choi Chong-Hyuk, Kyung Hee-Soo, Lee Ju-Hong, Yoo Jae Doo, Yoo Ju-Hyung, Choi Choong-Hyeok, Kim Chang-Wan, Kim Hee-Chun, Oh Kwang-Jun, Bin Seong-Il, Lee Myung Chul
Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, South Korea.
Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-gu, Seoul, South Korea.
BMC Musculoskelet Disord. 2017 May 26;18(1):223. doi: 10.1186/s12891-017-1591-4.
This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis.
Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption.
Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified.
This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis.
ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.
本随机、双盲、多中心、非劣效性试验旨在评估交联透明质酸盐（XLHA，单次注射剂型）与线性高分子量透明质酸盐（HMWHA，三次注射剂型）用于有症状的膝关节骨关节炎患者时的疗效和安全性。
287例骨关节炎患者（Kellgren-Lawrence分级I至III级）被随机分入每组。两组均每周注射3次，但在XLHA注射前先注射2次生理盐水以维持双盲。主要终点是最后一次注射后12周时负重疼痛（WBP）的变化。次要终点包括西安大略和麦克马斯特大学骨关节炎指数；患者和研究者的整体评估；静息、夜间或活动时的疼痛；OMERACT-OARSI应答率；WBP至少降低20 mm或40%的患者比例；以及急救药物的使用频率及其总消耗量。
最后一次注射后12周时，XLHA组WBP的平均变化为-33.3 mm，HMWHA组为-29.2 mm，证明XLHA不劣于HMWHA，因为95% CI的下限（-1.9 mm，10.1 mm）远高于预先设定的界值（-10 mm）。所有次要终点在组间均无显著差异。注射部位疼痛是最常见的不良事件，未发现明显的安全问题。
本研究表明，单次注射XLHA在减轻WBP方面不劣于每周3次注射HMWHA，并支持XLHA作为膝关节骨关节炎的一种有效且安全的治疗方法。
ClinicalTrials.gov（NCT01510535）。本试验于2012年1月6日注册。
