Abstract
INTRODUCTION: Some argued that clinical efficacy of Chondroitin Sulfate (CS) could vary upon the product origin. The objective of this trial is to compare the effect of 2 CS medicinal products from different origin: Structum(®) (avian, 1000mg/day) and Chondrosulf(®) (bovine, 1200mg/day). METHODS: This was a randomized, double-blind, double placebo, active-controlled, parallel-group study using a non-inferiority design. Symptomatic osteoarthritis of the knee patients, according to American College of Rheumatology criteria, aged 50-80 years received either Structum(®) (500mg BID) or Chondrosulf(®) (400mg TID) during 24 weeks. Inclusion criteria were: global pain in the target knee ≥ 40mm on a Visual Analog Scale (VAS 0-100), a Lequesne's Algofunctional Index (LFI) score ≥ 7 (range: 0-24) and a radiological Kellgren-Lawrence grade 2 or 3. Primary outcome was the mean change over 24 weeks of pain VAS and LFI score. Secondary outcomes were patient's and physician's global assessments, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate, analgesics intake and Medical Outcomes Survey Short-Form 12 (SF-12). Safety was assessed by recording adverse events. A non-inferiority test was performed on the Structum(®)-Chondrosulf(®) difference for VAS and LFI score changes. Predefined non inferiority limit was settled as the lower limit of the 95% CI above -5mm and -1pt for pain VAS and LFI score respectively. RESULTS: 837 patients were randomized: 817 available for the full analysis dataset (FAS), 692 for the per protocol (PP) analysis. No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups. PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks. Mean Pain VAS decreased by 23.9mm (17.5) in Structum(®) group and 23.8mm (17.2) in Chondrosulf(®) group (difference: 0.012 [CI95%: -2.6 ; 2.6]). Mean LFI score decreased by 3.2 (2.4) and 3.1 (2.4) respectively (difference: 0.139 [CI95%: -0.2 ; 0.5]). The lower limits of the 2 CI were above predefined non inferiority margin, which demonstrated the non inferiority of Structum(®) in comparison with Chondrosulf(®). FAS analysis gave similar results. Secondary efficacy outcomes analysis showed the same trends. Responders rate were 76.3% and 73.8% respectively (PP, W24). Treatments were well tolerated: 2.4% in Structum(®) group and 4.5% in Chondrosulf(®) group withdrew from the study for safety reasons. CONCLUSION: Structum(®) and Chondrosulf(®) were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients, without any safety concerns. TRIAL REGISTRATION: http://www.controlled-trials.com Number: ISRCTN04305346.