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

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.

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