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.
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Funding This was a trial conducted for regulatory purposes and therefore received full financial support from the sponsor Rottapharm|Madaus. Co-authors SC, MD, GG and LCR are scientists from the Department of Clinical Pharmacology of Rottapharm|Madaus and agreed individually to be listed as co-authors due to their involvement in the study; there was no other involvement of the sponsor as a corporate entity in the conduct of the study and in the manuscript submission process. Co-authors FB and JG were the study principal investigators and received research grants for this. Co-authors FB, XC, FR and EM received a reimbursement fee for their involvement in the steering committee of the study.
Competing interests Rottapharm|Madaus is the sponsor of the study and the manufacturer of one of the preparations tested in this study (GO-ON) and has this preparation on the market in different countries of the world. The full trial protocol, all study documents including completed case record forms and the complete statistical database are available from the sponsor's good clinical practice archives.
Ethics approval Ethics approval was provided by the Comité de Protection des Personnes, AP-HP St-Antoine Hospital, Paris and the ethics committee of Regensburg University and by all applicable local ethics committees.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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