Efficacy and safety of a combination of platelet-rich plasma with non-crosslinked hyaluronic acid versus a crosslinked hyaluronic acid, in single-injection for knee osteoarthritis. Randomized, controlled, multicenter, non-inferiority trial

The potential synergistic effects of the combination of Platelet Rich Plasma with hyaluronic acid remain insufficiently evaluated in randomized controlled trials in symptomatic knee osteoarthritis. A single-blind intention-to-treat randomized controlled non-inferiority trial was conducted to compared efficacy and safety of a combination of autologous platelet-rich plasma with non-crosslinked hyaluronic acid (PRP-HA) prepared with Cellular Matrix technology (Cellular Matrix A-CP-HA Kit) versus Synvisc-One, a crosslinked hyaluronic acid (HA), in single-injection for moderate knee osteoarthritis with follow-up at 1, 3 and 6 months (WOMAC, SF36). Secondary outcome was to evaluate the percentage of responders at 6 months (OMERACT-OARSI, PASS and WOMAC pain MCII). A 6-month open-label extension phase with a single injection of PRP-HA was offered to patients still symptomatic at 6 months from both groups. 156 patients were included. Regarding the non-inferiority test, a significant difference between the two groups was demonstrated for the WOMAC pain score on walking at M6, in favor of PRP-HA (-6.34 [-12.51; -0.18], p = 0.04). The percentage of responders in favor of PRP-HA at 6 months was higher for PASS WOMAC Pain (50.6% vs. 33.3%, p = 0.04), whereas no significant differences were found for the OMERACT–OARSI (58% vs. 48%, p = 0.26) and MCII (44.4% vs. 36.0%, p = 0.29) criteria. In the extension phase with PRP-HA, a significant improvement in WOMAC was observed at 12 months, compared with baseline values in both groups. The combination of PRP with non-crosslinked HA in mono-injection was found to be non-inferior to crosslinked HA, with regards to the percentage of responders over 6 months (WOMAC pain). It also demonstrated a good safety profile in symptomatic knee osteoarthritis. The clinical trial “Cellular Matrix Device for the Treatment of Mild to Moderate Knee Osteoarthritis” was registered under the trial registration number NCT03328728 on 24 October 2017. The registration was performed retrospectively, as the first patient was enrolled earlier, on 18 July 2017 the primary endpoint and analysis plan were prespecified and unchanged.