A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis

Abstract

Objectives: 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.

Figure 1

Trial profile.

Figure 2

Intention-to-treat mean (and SE) change from baseline at each assessment time point for the Western Ontario and McMaster Universities pain subscale score in the two groups receiving GO-ON (n=217) or Hyalgan (n=209). The arrows indicate the intra-articular injections.

Figure 3

Point estimate and 95% CI of the difference (GO-ON vs Hyalgan, in mm) in the primary outcome represented by the Western Ontario and McMaster Universities pain subscale mean improvement. Values are differences in mean changes between GO-ON and Hyalgan at 6 months after treatment in the per-protocol (PP) and intention-to-treat (ITT) populations (−9 mm was the non-inferiority margin).