Clinical trial NCT02266433: Dexamethasone Versus Ketorolac Injection for the Treatment of Local Inflammatory Hand and Upper Extremity Disorders
Official title: A Double-blinded, Prospective, Randomized, Controlled Trial Comparing Dexamethasone Versus Ketorolac Injection for the Treatment of Local Inflammatory Hand and Upper Extremity Disorders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: DeQuervains Tenosynovitis
Lateral Epicondylitis
Tennis Elbow
Trigger Finger
Tenosynovitis
Inflammatory Disease
Keywords: DeQuervains Tenosynovitis
Lateral Epicondylitis
Tennis Elbow
Trigger Finger
Tenosynovitis
Inflammatory Disease
Dexamethasone
Ketorolac
Toradol
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2014-10-17
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to compare local corticosteroid hand and elbow injections to placebo or ketorolac to determine if there is an equal or better reduction of symptoms for common orthopaedic upper extremity disorders including: De Quervain's tenosynovitis, trigger fingers, and tennis elbow (lateral epicondylitis). The investigators will enroll 780 subjects, divided equally into three arms for each disease process, and compare the efficacy of Ketorolac injections to Dexamethasone injections by measuring patient's functional status scores and pain scores at 0 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 month followup periods, prospectively over time.

Detailed description: Objectives: The primary objective of this study is to compare local corticosteroid hand and elbow injections to placebo or ketorolac to determine if there is an equal or better reduction of symptoms for common orthopaedic upper extremity disorders including: De Quervain's tenosynovitis, trigger fingers, and tennis elbow (lateral epicondylitis).

Number of Subjects: 780 total subjects:

• 260 subjects in each of the 3 treatment groups (De Quervain's tenosynovitis, trigger fingers and lateral epicondylitis) Diagnosis and Main Inclusion Criteria Subjects 18 years or older, with any of the following diagnoses: De Quervain's tenosynovitis, trigger fingers, or lateral epicondylitis

Study Product, Dose, Route, Regimen: Peritendinous soft tissue injection for De Quervain's tenosynovitis, trigger fingers and lateral epicondylitis:

• 1 mL of ketorolac (30mg/mL) and 0.5 mL (5mg) of 1% lidocaine Duration of administration Single administration, with a second injection permitted only once as subject desires due to no major clinical response at the 4 or 8-week follow-up.

Reference therapy: Standard of care peritendinous soft tissue injection for De Quervain's tenosynovitis, trigger fingers, and lateral epicondylitis:

• 1 mL of dexamethasone sodium phosphate (4mg/mL) and 0.5 mL (5mg) of 1% lidocaine

Statistical Methodology: The sample size as stated above was derived by a power analysis. A power analysis indicated that a total sample size of 200 patients randomized equally (1:1 randomization) to each treatment arm (i.e trigger finger, De Quervain's disease, and tennis elbow) without any blocking or stratification would provide 80% statistical power (alpha=.05, beta=0.20) to detect a 10% difference in mean Quick Disabilities of the Arm, Shoulder and Hand (quickDASH) scores between cohorts assuming a common standard deviation of 25% (effect size = 10/25 = 0.4). To account for an estimated 30% loss to follow-up, the investigators plan to enroll a total of 260 patients per treatment arm (i.e. trigger finger, De Quervain's disease, and tennis elbow). In total, there will be approximately 780 patients enrolled among all treatment arms.

1.1 Background Many orthopaedic hand disorders are comprised of different forms of tendonitis, tenosynovitis, and arthritis. The inflammatory processes of these disorders cause discomfort and functional impairment for patients. Decreasing the inflammatory response by use of splinting, physiotherapy, systemic anti-inflammatory agents, and local anti-inflammatory injections helps to alleviate some or all of the discomfort (2-4). Steroid injections are not entirely benign, and complications include tendon ruptures, subcutaneous fat atrophy, skin pigmentation changes, cartilage damage, and hyperglycemic responses in diabetics (9-11, 22-23). Studies have shown that ketorolac, a non-steroidal anti-inflammatory agent has a potent anti-inflammatory effect comparable to corticosteroids and a strong analgesic effect allowing for reduced opioid consumption postoperatively (7, 8). One could argue that the potent anti-inflammatory properties of ketorolac could be used to substitute for local corticosteroid injections in treating certain hand disorders. Given the side-effect profile for corticosteroids it may be beneficial to treat inflammatory disorders with local ketorolac injections. Nonsteroidal anti-inflammatory agents also have their known systemic adverse effects including gastric ulceration and intestinal bleeding as well as impairment of renal function. Most of these side effects are theoretically avoided with local tissue injections.

1.2 Study Drugs

Ketorolac:

The proposed use of ketorolac in this study is outside of the FDA-approved indication and is the investigational agent in this study

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID). The approved indication for Ketorolac is for the short-term (≤5 days) management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. It is highly protein bound (99%) and is largely metabolized by the liver. In it's approved indication it is contraindicated for those with renal impairment, active peptic ulcer disease, pregnant or nursing females, individuals with NSAID hypersensitivity, or individuals at high risk for bleeding/clotting disorders.

Dexamethasone:

Dexamethasone is a synthetic corticosteroid and possesses glucocorticoid activity, and will be used within its labeled indication for this study: intra-articular or soft tissue injection for: synovitis of osteoarthritis, epicondylitis, acute nonspecific tenosynovitis. It is the active comparator in this study.

In its approved indication there use limitations for immunocompromised individuals, pregnant females, persons with allergy to steroids, individuals with systemic fungal infections, and individuals with cerebral malaria. It is contra-indicated in systemic fungal infections, and hypersensitivity to any component of this product, including sulfites.

Lidocaine:

Lidocaine is a local anesthetic of the amide type, and will be used within its labeled indication for this study: production of local or regional anesthesia by infiltration techniques such as percutaneous injection. It is to be given as concomitant therapy with both the investigational agent, ketorolac injection, and the standard of care therapy, dexamethasone injection.

Eligibility criteria: Inclusion Criteria:

* Patients must be diagnosed with at least one of the following: trigger finger, de quervain's tenosynovitis, or tennis elbow (lateral epicondylitis)
* Patients age 18 years of age or older from all racial/ethnic types
* Patient who are both males and females
* Study participants will include any New York University employee or students as these individuals also can get hand and upper extremity pathology. It will be specifically reiterated to them that their academic status or grades, or employment will not be affected by their decision to participate in this study. Record of the participation cannot be linked to an academic record.

Exclusion Criteria:

* Patients had previous steroid injection at the site in question within 90 days of enrollment
* Patients with a history of gastric ulcers, renal impairment, allergy/hypersensitivity to non-steroidal anti-inflammatory (NSAID) or lidocaine derivative medications, immunocompromised patients (HIV/AIDs) and pregnant females

Primary outcomes:
measure: Trigger Finger Treatment Group: EQVAS Score
timeFrame: Baseline
measure: Trigger Finger Treatment Group: EQVAS Score
timeFrame: 4 weeks
measure: Trigger Finger Treatment Group: EQVAS Score
timeFrame: 8 weeks
measure: Trigger Finger Treatment Group: EQVAS Score
timeFrame: 12 weeks
measure: Trigger Finger Treatment Group: EQVAS Score
timeFrame: 6 months
measure: Trigger Finger Treatment Group: QuickDASH Functional Scores
timeFrame: Baseline
measure: Trigger Finger Treatment Group: QuickDASH Functional Scores
timeFrame: 4 weeks
measure: Trigger Finger Treatment Group: QuickDASH Functional Scores
timeFrame: 8 weeks
measure: Trigger Finger Treatment Group: QuickDASH Functional Scores
timeFrame: 12 weeks
measure: Trigger Finger Treatment Group: QuickDASH Functional Scores
timeFrame: 6 months
measure: Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score
timeFrame: Baseline
measure: Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score
timeFrame: 4 weeks
measure: Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score
timeFrame: 8 weeks
measure: Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score
timeFrame: 12 weeks
measure: Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score
timeFrame: 6 months
measure: Trigger Finger Treatment Group: VAS Pain Scores
timeFrame: Baseline
measure: Trigger Finger Treatment Group: VAS Pain Scores
timeFrame: 4 weeks
measure: Trigger Finger Treatment Group: VAS Pain Scores
timeFrame: 8 weeks
measure: Trigger Finger Treatment Group: VAS Pain Scores
timeFrame: 12 weeks
measure: Trigger Finger Treatment Group: VAS Pain Scores
timeFrame: 6 months
measure: Trigger Finger Treatment Group: Quinnell Grading Scores
timeFrame: Baseline
measure: Trigger Finger Treatment Group: Quinnell Grading Scores
timeFrame: 4 weeks
measure: Trigger Finger Treatment Group: Quinnell Grading Scores
timeFrame: 8 weeks
measure: Trigger Finger Treatment Group: Quinnell Grading Scores
timeFrame: 12 weeks
measure: Trigger Finger Treatment Group: Quinnell Grading Scores
timeFrame: 6 months
measure: DeQuervain's Treatment Group: EQ-VAS Score
timeFrame: Baseline
measure: DeQuervain's Treatment Group: EQ-VAS Score
timeFrame: 4 weeks
measure: DeQuervain's Treatment Group: EQ-VAS Score
timeFrame: 8 weeks
measure: De Quervain's Treatment Group: QuickDASH Scores
timeFrame: Baseline
measure: De Quervain's Treatment Group: QuickDASH Scores
timeFrame: 4 weeks
measure: De Quervain's Treatment Group: QuickDASH Scores
timeFrame: 8 weeks
measure: DeQuervain's Treatment Group: EQ-5D Score
timeFrame: Baseline
measure: DeQuervain's Treatment Group: EQ-5D Score
timeFrame: 4 weeks
measure: DeQuervain's Treatment Group: EQ-5D Score
timeFrame: 8 weeks
measure: De Quervain's Treatment Group: VAS Pain Score
timeFrame: Baseline
measure: De Quervain's Treatment Group: VAS Pain Score
timeFrame: 4 weeks
measure: De Quervain's Treatment Group: VAS Pain Score
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) Over Lateral Epicondyle
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) in Lateral Epicondyle
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) Over Lateral Epicondyle
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) With Resisted Wrist Extension
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) With Resisted Wrist Extension
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) With Resisted Wrist Extension
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: QuickDASH Functional Scores
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: QuickDASH Functional Scores
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: QuickDASH Functional Scores
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: EQ-5D Scores
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: EQ-5D Scores
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: EQ-5D Scores
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: VAS Pain Score
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: VAS Pain Score
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: VAS Pain Score
timeFrame: 8 weeks
measure: Lateral Epicondylitis Treatment Group: EQ-VAS Score
timeFrame: Baseline
measure: Lateral Epicondylitis Treatment Group: EQ-VAS Score
timeFrame: 4 weeks
measure: Lateral Epicondylitis Treatment Group: EQ-VAS Score
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University School of Medicine
state: New York
Study officials:
affiliation: NYU Hospital for Joint Diseases; NYULMC
name: Anthony Sapienza, MD
role: PRINCIPAL_INVESTIGATOR
References: