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.

Mahidol University

Status and phase

Completed

Phase 3

Conditions

Adhesive Capsulitis of the Shoulder

Treatments

Drug: Intra-articular Hyaluronic Acid and Ketorolac

Drug: Intra-articular Ketorolac

Study type

Interventional

Funder types

Other

Identifiers

NCT07183436

MURA2023/497

Details and patient eligibility

About

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.

Full 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.

Enrollment

56 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Eligible participants were adults diagnosed with adhesive capsulitis defined by limitation of shoulder motion ≥25 degrees in at least two planes compared to the contralateral side

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