title: Safety and efficacy of intra-articular injections of a combination of hyaluronic acid and mannitol (HAnOX-M) in patients with symptomatic knee osteoarthritis: Results of a double-blind, controlled, multicenter, randomized trial.
abstract: BACKGROUND
  To compare both safety and efficacy of a novel intra-articular viscosupplement made of intermediate molecular weight (MW) hyaluronic acid (HA) mixed with high concentration of mannitol with a marketed high MW HA, in patients with knee osteoarthritis (OA).
  
  
  METHODS
  Patients with symptomatic knee OA, with radiological OARSI grades 1 to 3, were enrolled in a controlled, double-blind, parallel-group, non-inferiority trial. They were randomized to receive three intra-articular injections, at weekly intervals, of either HAnOX-M made of a combination of HA (MW one to 1.5MDa, 31mg/2ml) and mannitol (70mg/2ml) or Bio-HA (MW 2.3 to 3.6MDa, 20mg/2ml). The primary outcome was six-month change in the WOMAC pain subscale (0 to 20). Sample size was calculated according to a non-inferiority margin of 1.35. Secondary endpoints included six-month change in function and walking pain, analgesic consumption and safety.
  
  
  RESULTS
  The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 205 and 171 patients. HAnOX-M and Bio-Ha groups did not differ statistically at baseline. The primary analysis was conducted in the PP population, then in the ITT population. The average WOMAC pain score at baseline was 9.5 in both groups. Mean (SD) variations in WOMAC pain score were -4.4 (3.8) and -4.5 (4.3) mm, for HAnOX and Bio-HA respectively, satisfying the claim for non-inferiority. Similar results were obtained for all other secondary endpoints.
  
  
  CONCLUSIONS
  Treatment with of HAnOX-M is effective to alleviate knee OA symptoms and to improve joint function over six months, with similar safety than conventional HA viscosupplement.
authors.affiliation: Department of Rheumatology, Hôpital Nord Franche-Comté, Belfort, France. Electronic address: thierry.conrozier@hnfc.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Conrozier
authors.affiliation: Department of Rheumatology, Hôpital Henri Mondor, Creteil, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Eymard
authors.affiliation: Department of Rheumatology, Hôpital Emile Muller, Mulhouse, France.
authors.forename: Naji
authors.initials: N
authors.lastname: Afif
authors.affiliation: Department of Rheumatology, Hôpital Nord Franche-Comté, Belfort, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Balblanc
authors.affiliation: Institut de l'Appareil Locomoteur Nollet, Paris, France; Hôpital Universitaire Pitié-Salpêtrière, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Legré-Boyer
authors.affiliation: Department of Rheumatology, Hôpital Henri Mondor, Creteil, France; Paris XII University, UPEC, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Chevalier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D016896:Treatment Outcome; D055675:Viscosupplements / Q000008:administration & dosage*
chemical_list: D055675:Viscosupplements; D008353:Mannitol; D006820:Hyaluronic Acid
keywords: Controlled trial; Hyaluronic acid; Intra-articular injection; Knee osteoarthritis; Mannitol; Viscosupplementation