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.

Not Applicable

Completed

• Conditions: Adhesive Capsulitis of the Shoulder
• Interventions: Drug: Intra-articular Hyaluronic Acid and Ketorolac; Drug: Intra-articular Ketorolac

• Registration Number: NCT07183436
• Lead Sponsor: Mahidol University

Brief 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.

Study Timeline

• Study Start: 2023-11-01
• Primary Completion: 2025-07-01
• Study Completion: 2025-07-01
• Status Verified: 2025-09
• Study First Submitted: 2025-09-14
• Study First Submitted QC: 2025-09-14
• Study First Posted: 2025-09-19
• Last Update Submitted: 2025-09-22
• Last Update Posted: 2025-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Adults aged 18-70 years
• Symptom duration of 1-12 months
• Provision of informed consent.

Exclusion Criteria

• History of trauma or prior surgery to the affected shoulder
• Bilateral adhesive capsulitis
• Uncontrolled diabetes (HbA1C > 7%)
• Abnormal thyroid function
• Prior intra-articular injection in the affected shoulder
• Full-thickness rotator cuff tear on imaging
• History of gastrointestinal bleeding
• Known allergy to hyaluronic acid or NSAIDs
• Systemic conditions affecting joint pain (e.g., SLE, rheumatoid arthritis, osteoarthritis)
• Neurological disorders affecting muscle strength or sensation coagulopathy or bleeding disorders withdrawal or refusal of consent at any time

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hyaluronic Acid and Ketorolac injection	Intra-articular Hyaluronic Acid and Ketorolac	Participants received a single intra-articular injection of Hyaluronic Acid and Ketorolac
Ketorolac injection	Intra-articular Ketorolac	Participants received a single intra-articular injection of ketorolac

Primary Outcome Measures

Name	Time	Method
Shoulder function (Thai SPADI score)	Baseline, 2, 6, 12, and 24 weeks post-injection	Shoulder Pain and Disability Index (Thai version), patient-reported outcome measure, score range 0-100 (higher score = worse disability)

Secondary Outcome Measures

Name	Time	Method
Pain intensity (VAS score)	Baseline, 2, 6, 12, and 24 weeks post-injection	Visual Analog Scale for shoulder pain, 0-10 (higher score = worse pain)
Passive range of motion (PROM)	Baseline, 2, 6, 12, and 24 weeks post-injection	Passive range of motion of the affected shoulder (flexion, extension, abduction, adduction, internal and external rotation) measured with goniometer in degrees
Adverse events	0-24 weeks post-injection	Number and type of treatment-related adverse events (mild, moderate, or severe) reported by participants or observed by investigators

Trial Locations

Locations (1)

Faculty of Medicine Ramathibodi Hospital, Mahidol University; 🇹🇭 Bangkok, Thailand