Intra-articular injection of corticosteroid and hyaluronic acid is a common treatment for osteoarthritis of the knee. As a treatment drug for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of osteoarthritis and improve the function of the knee joint. However, there is no evidence regarding the efficacy of Intra-articular injection of corticosteroid and hyaluronic acid combined with duloxetine for pain management in patients with knee osteoarthritis. The aim of the study was to test the hypothesis that Intra-articular injection of corticosteroid plus hyaluronic acid combined with duloxetine could achieve superior pain management effects to Intra-articular injection of corticosteroid plus hyaluronic acid alone in patients undergoing knee osteoarthritis pain.

Inclusion Criteria:

• Participants meet American College of Rheumatology clinical and radiographic criteria for the diagnosis of knee osteoarthritis with knee pain [ pain for ≥14 days of each month for ≥3 months before study entry, with a mean score ≥4 on the 24-h average pain score (0-10) using the average of daily ratings before the trial]
• Body mass index < 40 kg/m2
• Radiographic criteria included Kellgren-Lawrence grade Ⅱ-III
• Knee stability, no deformity, no lumbar spondylosis with radiculopathy.
• Good cognition, and the ability to understand the study protocol and the agreement to participate.

Exclusion Criteria:

• Inflammatory arthritis, autoimmune disorder, septic arthritis, or any other concomitant disease (such as liver and kidney disease)
• Those who prior synovial fluid analysis indicative of a diagnosis other than osteoarthritis
• Participants with contraindications to duloxetine (currently using monoamine oxidase inhibitors, poorly controlled angle-closure glaucoma), previous exposure to duloxetine, combined with other drugs acting on the central nervous system (such as benzodiazepines) and allergic to any of the medications used in this study.
• With metabolic diseases or anticoagulation therapy
• Participants who had received invasive treatments to the knee during the past 6 months; joint replacement of the knee at any time or current infection in the affected limb.

Individual participant data that underlie the results reported in this article will be shared after deidentification.

The date will be shared from 6 months to 5 years following article publication.

An independent review committee will be responsible for reviewing applications and purposes from investigators. The datasets used and/or analysed during the current study will be available from the corresponding author on reasonable request once the study has been completed.

This is a prospective, randomized, open-label blind endpoint (PROBE) study