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Completed

NCT Number: 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.

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.

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Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: 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.

Other names: Ketorolac injection

Primary outcomes

  1. Shoulder function (Thai SPADI score)

    Time frame: 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 outcomes

  1. Pain intensity (VAS score)

    Time frame: Baseline, 2, 6, 12, and 24 weeks post-injection

    Visual Analog Scale for shoulder pain, 0-10 (higher score = worse pain)

  2. Passive range of motion (PROM)

    Time frame: 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

  3. Adverse events

    Time frame: 0-24 weeks post-injection

    Number and type of treatment-related adverse events (mild, moderate, or severe) reported by participants or observed by investigators

Sponsors and collaborators

Lead sponsor

Mahidol University

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Sep 19, 2025
Registry last updated
Sep 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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