Dexamethasone Versus Ketorolac Injection for the Treatment of Local Inflammatory Hand and Upper Extremity Disorders

Phase 3

Terminated

Conditions: Lateral Epicondylitis
DeQuervains Tenosynovitis
Trigger Finger
Inflammatory Disease
Tennis Elbow
Tenosynovitis

Interventions: Drug: Dexamethasone
Drug: Ketorolac

Registration Number: NCT02266433

Lead Sponsor: NYU Langone Health

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 245

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm Receiving Dexamethasone Injection	Dexamethasone	Dexamethasone will be administered as a peritendinous soft tissue injection of 1 mL of dexamethasone sodium phosphate (4mg/mL) and 0.5 mL (5mg) of 1% lidocaine. Dexamethasone will be administered as a peritendinous soft tissue injection of 1 mL of dexamethasone sodium phosphate (4mg/mL) and 0.5 mL (5mg) of 1% lidocaine Patients will be followed at the initial office visit, 4-weeks, 8-weeks, 12-weeks, and 6 months post injection to determine clinical response. A second injection can be given only once if the patient desires due to no clinical response at the 4 or 8-week follow-up.
Arm Receiving Ketorolac Injection	Ketorolac	Ketorolac will be administered as a peritendinous soft tissue injection of 1 mL of ketorolac (30mg/mL) and 0.5 mL (5mg) of 1% lidocaine. Patients will be followed at the initial office visit, 4-weeks, 8-weeks, 12-weeks, and 6 months post injection to determine clinical response. A second injection can be given only once if the patient desires due to no clinical response at the 4 or 8-week follow-up.

Primary Outcome Measures

Name	Time	Method
Trigger Finger Treatment Group: QuickDASH Functional Scores	6 months	The QuickDASH (Quick - Disabilities of the Arm, Shoulder and Hand) is an 11-question standardized survey used to assess a patient's overall functional status and is widely used in the practice of orthopaedic surgery as an analog measurement of a patient's functional ability. Scores range from 0-100, with 100 being the most poor functionality and 0 being the best. This will be assessed at every visit by having the patient fill out the survey and our team calculating the score at the end of the visit.
DeQuervain's Treatment Group: EQ-VAS Score	8 weeks	The EuroQol-visual analogue scale (EQ-VAS) is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.
DeQuervain's Treatment Group: EQ-5D Score	8 weeks	The EQ-5D (EuroQol five-dimension scale) is a 5 question survey with 3 potential responses per question, based on measuring a patient's overall quality of life. The responses are compiled into a numerical score ranging from 1 to -0.11, with 1 being the best and -0.11 being the worst in terms of quality of life. This survey will be administered to patients at each visit, along with the other surveys.
De Quervain's Treatment Group: VAS Pain Score	8 weeks	VAS (Visual Analogue Scale) pain score is a 0-10 numerical score assessing patient's subjective level of reported pain. The higher the score, the higher and worse the pain level. This will be recorded from the patient's written response at every visit.
Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) Over Lateral Epicondyle	8 weeks	Clinician will examine the patient and palpate over the lateral epicondyle. Presence of pain is a positive test, recorded as 1. Absence of pain is a negative test, recorded as 0. This is done at every visit.
Trigger Finger Treatment Group: Quinnell Grading Scores	6 months	The Quinnell grading system monitors for trigger symptom improvement with a range of 0 (minimum) to 4 (maximum) with a higher number corresponding to worse symptoms: 0-normal movement of finger; 1-uneven movement; 2-active correctible locking of digit; 3-passively correctible locking; 4-fixed deformity.
Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) in Lateral Epicondyle	4 weeks	Clinician will examine the patient and palpate over the lateral epicondyle. Presence of pain is a positive test, recorded as 1. Absence of pain is a negative test, recorded as 0. This is done at every visit.
De Quervain's Treatment Group: QuickDASH Scores	8 weeks	The QuickDASH (Quick - Disabilities of the Arm, Shoulder and Hand) is an 11-question standardized survey used to assess a patient's overall functional status and is widely used in the practice of orthopaedic surgery as an analog measurement of a patient's functional ability. Scores range from 0-100, with 100 being the most poor functionality and 0 being the best. This will be assessed at every visit by having the patient fill out the survey and our team calculating the score at the end of the visit.
Lateral Epicondylitis Treatment Group: EQ-5D Scores	8 weeks	The EQ-5D (EuroQol five-dimension scale) is a 5 question survey with 3 potential responses per question, based on measuring a patient's overall quality of life. The responses are compiled into a numerical score ranging from 1 to -0.11, with 1 being the best and -0.11 being the worst in terms of quality of life. This survey will be administered to patients at each visit, along with the other surveys.
Trigger Finger Treatment Group: EQVAS Score	6 months	The EuroQol-visual analogue scale (EQ-VAS) is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.
Trigger Finger Treatment Group: EuroQuol-5D (EQ-5D) Functional Score	6 months	The EQ-5D (EuroQol five-dimension scale) is a 5 question survey with 3 potential responses per question, based on measuring a patient's overall quality of life. The responses are compiled into a numerical score ranging from 1 to -0.11, with 1 being the best and -0.11 being the worst in terms of quality of life. This survey will be administered to patients at each visit, along with the other surveys.
Trigger Finger Treatment Group: VAS Pain Scores	6 months	VAS (Visual Analogue Scale) pain score is a 0-10 numerical score assessing patient's subjective level of reported pain. The higher the score, the higher the pain level. This will be recorded from the patient's written response at every visit.
Lateral Epicondylitis Treatment Group: VAS Pain Score	8 weeks	VAS (Visual Analogue Scale) pain score is a 0-10 numerical score assessing patient's subjective level of reported pain. The higher the score, the higher and worse the pain level. This will be recorded from the patient's written response at every visit.
Lateral Epicondylitis Treatment Group: EQ-VAS Score	8 weeks	The EQ-VAS (EuroQol visual analog scale) is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.
Lateral Epicondylitis Treatment Group: Participants With Pain (Positive Test) With Resisted Wrist Extension	8 weeks	The clinician examines the patient and asks patient to extend wrist against resistance by the clinician. Production of pain is a positive test, recorded as 1. Absence of pain is a negative test, recorded as 0. This is done at every visit.
Lateral Epicondylitis Treatment Group: QuickDASH Functional Scores	8 weeks	The QuickDASH (Quick - Disabilities of the Arm, Shoulder and Hand) is an 11-question standardized survey used to assess a patient's overall functional status and is widely used in the practice of orthopaedic surgery as an analog measurement of a patient's functional ability. Scores range from 0-100, with 100 being the most poor functionality and 0 being the best. This will be assessed at every visit by having the patient fill out the survey and our team calculating the score at the end of the visit.