Efficacy of the combination therapy of platelet-rich plasma and hyaluronic acid on improving knee pain and dysfunction in patients with moderate-to-severe KOA: a protocol for a randomised controlled trial.

introduction54% of patients with moderate-to-severe knee osteoarthritis (KOA) still reported persistent pain and functional loss after conservative treatment according to guidelines. As an emerging treatment, platelet-rich plasma (PRP) has been proven to significantly relieve pain and improve activity function in patients with mild-to-moderate KOA, either used alone or in combination with hyaluronic acid (HA). However, it is still unclear of its efficacy in moderate-to-severe KOA. This study aims to evaluate the clinical efficacy of PRP and the combination therapy of PRP and HA in patients with moderate-to-severe KOA and to explore the potential synergistic effect of PRP and HA. METHODS AND ANALYSIS: This triple-blind randomised controlled trial will involve a total of 162 participants with moderate-to-severe KOA from two study centres. Participants will be allocated randomly into three groups: the HA group, the PRP group and the combination (PRP+HA) group and, respectively, receive HA (2.5 mL)+saline (3 mL)/PRP (3 mL)+saline (2.5 mL)/PRP (3 mL)+HA (2.5 mL) intra-articular injection each week for 4 consecutive weeks. All of the injections will be performed under the guidance of ultrasound. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 6 months, and secondary outcomes include the change of ultrasound images (suprapatellar bursa effusion and synovitis), Timed Up and Go test and 12-Item Short-Form Health Survey. All outcomes will be evaluated at baseline and 1-month, 3-month and 6-month follow-ups. Data will be analysed on intention-to-treat principles and a per-protocol basis. ETHICS AND DISSEMINATION: This protocol was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (reference number (2021)-02-231-02). The study results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100050974.