title: A double-blind, randomized, saline-controlled study of the efficacy and safety of EUFLEXXA for treatment of painful osteoarthritis of the knee, with an open-label safety extension (the FLEXX trial).
abstract: OBJECTIVE
  To report the FLEXX trial, the first well-controlled study assessing the safety and efficacy of Euflexxa (1% sodium hyaluronate; IA-BioHA) therapy for knee osteoarthritis (OA) at 26 weeks.
  
  
  METHODS
  This was a randomized, double-blind, multicenter, saline-controlled study. Subjects with chronic knee OA were randomized to 3 weekly intra-articular (IA) injections of either buffered saline (IA-SA) or IA-BioHA (20 mg/2 ml). The primary efficacy outcome was subject recorded difference in least-squares means between IA-BioHA and IA-SA in subjects' change from baseline to week 26 following a 50-foot walk test, measured via 100-mm visual analog scale (VAS). Secondary outcome measures included Osteoarthritis Research Society International responder index, Western Ontario McMaster University Osteoarthritis Index VA 3.1 subscales, patient global assessment, rescue medication, and health-related quality of life (HRQoL) by the SF-36. Safety was assessed by monitoring and reporting vital signs, physical examination of the target knee following injection, adverse events, and concomitant medications.
  
  
  RESULTS
  Five hundred eighty-eight subjects were randomized to either IA-BioHA (n = 293) or IA-SA (n = 295), with an 88% 26 week completion rate. No statistical differences were noted between the treatment groups at baseline. In the IA-BioHA group, mean VAS scores decreased by 25.7 mm, compared with 18.5 mm in the IA-SA group. This corresponded to a median reduction of 53% from baseline for IA-BioHA and a 38% reduction for IA-SA. The difference in least-squares means was -6.6 mm (P = 0.002). Secondary outcome measures were consistent with significant improvement in Osteoarthritis Research Society International responder index, HRQoL, and function. Both IA-SA and IA-BioHA injections were well tolerated, with a low incidence of adverse events that were equally distributed between groups. Injection-site reactions were reported by 1 (<1%) subject in the IA-SA group and 2 (1%) in the IA-BioHA group.
  
  
  CONCLUSIONS
  IA-BioHA therapy resulted in significant OA knee pain relief at 26 weeks compared with IA-SA. Subjects treated with IA-BioHA also experienced significant improvements in joint function, treatment satisfaction, and HRQoL.
authors.affiliation: Division of Rheumatology and Immunology, University of California Los Angeles, Los Angeles, CA 90095, USA. journals@royaltman.com
authors.forename: Roy D
authors.initials: RD
authors.lastname: Altman
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rosen
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bloch
authors.forename: Hind T
authors.initials: HT
authors.lastname: Hatoum
authors.forename: Paul
authors.initials: P
authors.lastname: Korner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000368:Aged; D018771:Arthralgia / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D010147:Pain Measurement; D011788:Quality of Life; D016896:Treatment Outcome; D014481:United States; D016138:Walking / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D006820:Hyaluronic Acid