Twelve-month efficacy of carboxymethyl-chitosan in refractory knee osteoarthritis: A randomized controlled trial (PIONEER).

Objectives: The 12-month efficacy and safety of a novel bioresorbable fluid implant based on CM-chitosan for intra-articular injection was evaluated in knee osteoarthritis (OA) patients with predictive factors of failure to viscosupplementation. Design: This pilot single-blind randomized controlled study was conducted in 104 patients with at least one of the following OA phenotypes: tricompartmental OA, patellofemoral involvement, K&L grade III or IV and/or body mass index >30 ​kg/m Results: At 6 months post-injection, mean WOMAC pain reduction vs. baseline was 69.4 ​± ​25.5 ​% for the CM-chitosan group and 66.3 ​± ​26.15 ​% for the Hylan G-F 20 group (non-inferiority p ​= ​0.096; 95 ​% CI -16.94 ​%, 7.02 ​%). At 12 months, significant symptomatic improvement in both groups, with clinically important differences in WOMAC pain reduction in favor of CM-chitosan, were observed, including in the subgroups of patients with patellofemoral OA (Δ 11.5 ​%), obese patients (Δ 21.7 ​%) and patients eligible for TKA at baseline (Δ 13.5 ​%). CM-chitosan showed a high response rate (93.8 ​%), as well as high patient (93.8 ​%) and investigator (90.6 ​%) satisfaction. No new safety signals were identified. Conclusions: In this difficult-to-treat population, CM-chitosan was non-inferior to Hylan G-F 20, but did show clinically important, though not statistically significant, differences in pain reduction at 12 months. CM-chitosan was effective in improving OA symptoms and physical function for 12 months.