title: Comparison of two hyaluronic acid formulations for safety and efficacy (CHASE) study in knee osteoarthritis: a multicenter, randomized, double-blind, 26-week non-inferiority trial comparing Durolane to Artz.
abstract: BACKGROUND
  Intra-articular injection of hyaluronic acid (HA) is often used as therapy for knee osteoarthritis because it is less expensive and less aggressive than total knee replacement. Therefore, it is important to document whether HA is safe and efficacious. We tested whether single and multiple injection viscosupplementation with HA is associated with clinically meaningful pain relief in a new randomized clinical trial (RCT). Our objective was to compare safety and efficacy of intra-articular HA in two formulations: one 3.0 ml injection of Durolane versus five 2.5 ml injections of Artz for the treatment of knee osteoarthritis pain.
  
  
  METHODS
  Patients (N=349) from the People's Republic of China were randomized to treatment (Durolane=175, Artz=174). The Durolane group received a 3.0 ml injection at week 0 (baseline), with sham skin punctures at weeks 1, 2, 3, and 4. The Artz group received one 2.5 ml injection at each of the same time points. The primary assessment tool was the Likert-type Western Ontario and McMaster University (WOMAC) pain scale at weeks 0, 6, 10, 14, 18, and 26. Secondary assessments were WOMAC physical function, knee stiffness, and global self-assessment, at identical time points. Statistically-controlled analyses were non-inferiority of Durolane over 18, then over 26 weeks, with a priori non-inferiority defined as 8% of the relevant scale. Acetaminophen was permitted as rescue analgesia and all adverse events (AEs) were recorded.
  
  
  RESULTS
  Overall study retention was excellent; 332 patients (95.1%) completed 18 weeks and 319 (91.4%) completed 26 weeks, with no significant retention difference between treatment arms. All variables met non-inferiority criteria over 18 and 26 weeks. Efficacy response in both arms was >90%. Treatment-related AEs were 9.8% (17/174) for Artz and 13.1% (23/175) for Durolane.
  
  
  CONCLUSIONS
  A single injection of Durolane is non-inferior to 5 injections of Artz over 18 and 26 weeks for pain, physical function, global self-assessment, and knee stiffness. Both treatments were efficacious, safe, and well tolerated.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01295580 . Registered 11 February 2011.
authors.affiliation: Arthritis Clinic & Research Center, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China. 469325342@qq.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, China. zhangke60@medmail.com.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shanghai 6th People's Hospital, Shanghai, China. zxl40@vip.sina.com.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shanghai 9th People's Hospital, Shanghai, China. zhuzhenan2006@126.com.
authors.forename: Zhenan
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Province, China. zrjwsj@zju.edu.cn.
authors.forename: Shigui
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, Beijing Military General Hospital, Beijing, China. suntiansheng_@163.com.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Beijing Friendship Hospital, Beijing, China. guoaij@yahoo.com.cn.
authors.forename: Ai
authors.initials: A
authors.lastname: Guo
authors.affiliation: Bioventus LLC, Durham, NC, USA. John.Jones@bioventusglobal.com.
authors.forename: John
authors.initials: J
authors.lastname: Jones
authors.affiliation: Bioventus LLC, Durham, NC, USA. Grant.Steen@bioventusglobal.com.
authors.forename: R Grant
authors.initials: RG
authors.lastname: Steen
authors.affiliation: TigerMed Consulting Co., Ltd, Beijing, China. bin.shan@tigermed.net.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.affiliation: TigerMed Consulting Co., Ltd, Beijing, China. jenny.zhang@tigermed.net.
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Arthritis Clinic & Research Center, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China. linjianhao@pkuph.edu.cn.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Lin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007719:Knee Joint; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D006820:Hyaluronic Acid