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.

NCT07183436 | Completed Phase 3 DMC

• 1 other identifier: MURA2023/497
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Adhesive Capsulitis of the Shoulder

Keywords

Adhesive capsulitis; Frozen shoulder; Shoulder pain; Hyaluronic acid; Ketorolac; Intra-articular injection; Randomized controlled trial; Range of motion

Outcome Measures

Primary Outcomes (1)

• Shoulder function (Thai SPADI score)

  Shoulder Pain and Disability Index (Thai version), patient-reported outcome measure, score range 0-100 (higher score = worse disability)

  Baseline, 2, 6, 12, and 24 weeks post-injection

Secondary Outcomes (3)

• Pain intensity (VAS score)

  Baseline, 2, 6, 12, and 24 weeks post-injection

• Passive range of motion (PROM)

  Baseline, 2, 6, 12, and 24 weeks post-injection

• Adverse events

  0-24 weeks post-injection

Study Arms (2)

Hyaluronic Acid and Ketorolac injection

EXPERIMENTAL

Participants received a single intra-articular injection of Hyaluronic Acid and Ketorolac

Drug: Intra-articular Hyaluronic Acid and Ketorolac

Ketorolac injection

ACTIVE COMPARATOR

Participants received a single intra-articular injection of ketorolac

Drug: Intra-articular Ketorolac

Interventions

Intra-articular Hyaluronic Acid and Ketorolac DRUG

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.

Also known as: Hyaluronic Acid and Ketorolac injection

Hyaluronic Acid and Ketorolac injection

Intra-articular Ketorolac DRUG

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.

Also known as: Ketorolac injection

Ketorolac injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (5)

• Lee SC, Rha DW, Chang WH. Rapid analgesic onset of intra-articular hyaluronic acid with ketorolac in osteoarthritis of the knee. J Back Musculoskelet Rehabil. 2011;24(1):31-8. doi: 10.3233/BMR-2011-0272.

  PMID: 21248398 RESULT

• Taheri P, Dehghan F, Mousavi S, Solouki R. Comparison of Subacromial Ketorolac Injection versus Corticosteroid Injection in the Treatment of Shoulder Impingement Syndrome. J Res Pharm Pract. 2017 Oct-Dec;6(4):223-227. doi: 10.4103/jrpp.JRPP_17_57.

  PMID: 29417082 RESULT

• Xu J, Qu Y, Li H, Zhu A, Jiang T, Chong Z, Wang B, Shen P, Xie Z. Effect of Intra-articular Ketorolac Versus Corticosteroid Injection for Knee Osteoarthritis: A Retrospective Comparative Study. Orthop J Sports Med. 2020 Apr 10;8(4):2325967120911126. doi: 10.1177/2325967120911126. eCollection 2020 Apr.

  PMID: 32313809 RESULT

• Mao B, Peng R, Zhang Z, Zhang K, Li J, Fu W. The Effect of Intra-articular Injection of Hyaluronic Acid in Frozen Shoulder: a Systematic Review and Meta-analysis of Randomized Controlled Trials. J Orthop Surg Res. 2022 Mar 3;17(1):128. doi: 10.1186/s13018-022-03017-4.

  PMID: 35241100 RESULT

• Uhm KE, Chang MC. Comparison of Effectiveness of Intraarticular Hyaluronate and Corticosteroid injections in Adhesive Capsulitis: A Systematic Review and Meta-analysis. Pain Physician. 2024 Sep;27(7):387-400.

  PMID: 39353107 RESULT

Related Links

• Randomized, double-blind, placebo-controlled trial of 60 patients with adhesive capsulitis. Participants were randomized into four arms (saline, corticosteroid, hyaluronic acid, corticosteroid + hyaluronic acid)

MeSH Terms

Conditions

Bursitis; Shoulder Pain

Interventions

Hyaluronic Acid; Ketorolac

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Arthralgia; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pratantat Charoenchaipong, MD

  Ramathibodi Hospital

  PRINCIPAL INVESTIGATOR

• Sorawut Thamyongkit, MD

  Chakri Naruebodindra Medical Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants randomized in a 1:1 ratio to receive either intra-articular HA+ketorolac or ketorolac alone, each followed by standardized rehabilitation

Study Record Dates

• First Submitted: September 14, 2025
• First Posted: September 19, 2025
• Study Start: November 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)