NCT07183436

Intra-articular Corticosteroids Are Widely Used for Adhesive Capsulitis, But Alternatives Are Required for Patients With Contraindications. Hyaluronic Acid (HA) and Ketorolac Have Shown Individual Benefits. However, Evidence on Their Combination Remains Limited.

Efficacy of Combined Intra-Articular Hyaluronic Acid and Ketorolac Versus Ketorolac Alone in the Treatment of Adhesive Capsulitis: A Randomized Controlled Trial

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 56 (actual)
• Sponsor: Mahidol University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This randomized, double-blind trial compared a single intra-articular injection of moderate-molecular-weight hyaluronic acid (HA) plus ketorolac with ketorolac alone in patients with adhesive capsulitis. Fifty-six participants were randomized into two equal groups and followed for 24 weeks. The primary outcome was shoulder function measured by the Thai Shoulder Pain and Disability Index (SPADI). Secondary outcomes included pain (VAS), passive range of motion (PROM), analgesic use, and adverse events. Both groups showed significant improvement in pain and function with no between-group difference in SPADI or VAS. The HA+ketorolac group demonstrated small but significant gains in external rotation and adduction. Both treatments were safe and well tolerated.

Detailed description

Adhesive capsulitis, or frozen shoulder, is characterized by pain and stiffness due to capsular inflammation and fibrosis. Corticosteroid injections are commonly used but may be contraindicated in some patients. Hyaluronic acid (HA) and ketorolac each have shown benefit, yet evidence on their combined use is limited. This randomized, double-blind, controlled trial enrolled 56 adults with adhesive capsulitis. Participants were randomized 1:1 to receive either HA plus ketorolac or ketorolac alone as a single intra-articular injection, followed by standardized rehabilitation. Follow-up assessments were conducted at 2, 6, 12, and 24 weeks. The primary outcome was functional outcome measured by the Thai SPADI. Secondary outcomes included pain (VAS), PROM, analgesic use, and adverse events. Both groups improved significantly in function and pain, without significant between-group differences. However, the HA+ketorolac group showed modest but significant improvements in external rotation and adduction range of motion. Safety outcomes were favorable in both groups, with only one mild adverse event reported. This study demonstrates that intra-articular HA combined with ketorolac and ketorolac alone are safe and effective alternatives to corticosteroid injection for adhesive capsulitis. The combination may provide additional benefit in range of motion recovery and can be considered in patients for whom corticosteroids are unsuitable.

Conditions

• Adhesive Capsulitis of the Shoulder

Interventions

Type	Name	Description
DRUG	Intra-articular Hyaluronic Acid and Ketorolac	Single intra-articular injection containing 2 mL moderate-molecular-weight hyaluronic acid (20 mg/2 mL), 1 mL ketorolac (30 mg/mL), and 2 mL lidocaine (10 mg/mL), total volume 5 mL. Administered under aseptic technique (ultrasound-guided or landmark-based) followed by standardized rehabilitation program.
DRUG	Intra-articular Ketorolac	single intra-articular injection containing 1 mL ketorolac (30 mg/mL), 2 mL lidocaine (10 mg/mL), and 2 mL normal saline, total volume 5 mL. Administered under aseptic technique (ultrasound-guided or landmark-based) followed by standardized rehabilitation program.

Timeline

• Start date: 2023-11-01
• Primary completion: 2025-07-01
• Completion: 2025-07-01
• First posted: 2025-09-19
• Last updated: 2025-09-25

Locations

1 site across 1 country: Thailand