title: A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis.
abstract: OBJECTIVE
  To compare the effects of an intermediate molecular weight (MW) intra-articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms.
  
  
  METHODS
  Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800-1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500-730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0-100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates
  
  
  RESULTS
  The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>-9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated.
  
  
  CONCLUSIONS
  Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety.
authors.affiliation: AP-HP Saint-Antoine Hospital, 184 rue du faubourg Saint-Antoine, 75012 Paris, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
authors.forename: Sara
authors.initials: S
authors.lastname: Cazzaniga
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amato
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Giacovelli
authors.forename: Xavier
authors.initials: X
authors.lastname: Chevalier
authors.forename: Francois
authors.initials: F
authors.lastname: Rannou
authors.forename: Lucio C
authors.initials: LC
authors.lastname: Rovati
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maheu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D055676:Viscosupplementation; D055675:Viscosupplements / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D055675:Viscosupplements; D006820:Hyaluronic Acid