Levobupivacaine Versus Liposomal Bupivacaine (Exparel®) for Treatment of Pain and Disability in Lateral Epicondylitis

Study Overview
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Brief Summary
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The main objective of the trial is to compare the effectiveness of injected levobupivacaine and liposomal bupivacaine in the treatment of pain and disability in patients with lateral epicondylitis. Primary outcome is pain (VAS) at 1 week and at 1 month after injection. Secondary outcomes are the Quick Disabilities of the Arm, Shoulder and Hand DASH (Quick DASH) and Oxford Elbow Score (OES) and a record of time off work due to lateral epicondylitis in days at 1 week and at 1 month. The study will be a cross-over trial

Detailed Description
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This project compares bupivacaine and long acting liposomal bupivacaine in the treatment of pain and disability related to lateral epicondylitis. The investigational medicinal products will be Chirocaine, ABBVIE OY, Espoo, Finland (levobupivacaine) and Exparel®, Pacira Pharmaceuticals, Inc., Parsippany, N.J. (liposomal bupivacaine). The design of the study will be an off-label, investigator initiated, randomized, controlled, double-Blind cross over treatment trial. Exparel (liposomal bupivacaine) will be the medicinal product in the intervention arm, whilst Chirocaine (levobupivacaine) will serve as the active control. Patients for the study will be recruited from the patients referred to the hand surgery outpatient clinic at Turku University Hospital, Finland. During the pilot phase of the study, four patients will be recruited, after which power analysis is done. The main study will include up to 50 patients, 25 patients in each study arm. Patient enrollment will start immediately after the all the relevant permits have been obtained (estimated September 2020). Normal distribution of data will be tested by Shapiro-Wilks test. The mean and Standard Deviation will be reported for normally distributed data. For data not distributed normally, the median and inter quartile ranges of the data will be reported. Independent samples t-test will be used for between-group comparison (normal distribution). The Mann-Whitney test will be used for non-normal data. The results will be published in a peer reviewed international academic journal.

Official Title
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Levobupivacaine Versus Liposomal Bupivacaine (Exparel®) for Treatment of Pain and Disability in Lateral Epicondylitis - Off-Label, Investigator Initiated Randomized, Controlled, Double-Blind Cross-Over Treatment Trial

Conditions
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Tennis Elbow, Lateral Epicondylitis

Intervention / Treatment
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* Drug: Liposomal bupivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent age 18-65 employed chronic lateral epicondylitis (duration >3 months) pain in lateral epicondyle pain in resisted wrist extension in elbow extension (Cozen test) X-ray or Magnetic resonance imaging (MRI) of the elbow (<12 months from enrollment) with no pathological findings other than lateral epicondylitis Exclusion Criteria: pregnancy, verbal confirmation from patient required unemployment allergy to levobupivacaine, bupivacaine or liposomal bupivacaine constant use of strong analgesics (e.g. opioids) other source of elbow pain (e.g. medial epicondylitis, distal biceps/triceps tendinitis) bilateral epicondylitis inability to give informed consent inability to understand the enrollment forms or to fill patient diary (forms are written in Finnish) previous injection treatment (e.g. cortisone, botulin toxin A, autologous plasma) for lateral epicondylitis during the past 3 months severe hepatic disease, or other underlying severe illness (cardiac failure, cancer, other systemic diseases)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The trial will be a crossover study. During the pilot phase, we will recruit up to 6 patients, after which we will do a power analysis. In the main study, up to 25 patients will be randomized into 2 groups. Group 1 will receive an injection af levobupivacaine (Chirocaine) into the lateral epicondylitis. The outcomes are assessed over the next month and then they are given the injection of liposomal bupivacaine (Exparel). Normal distribution of data will be tested by Shapiro-Wilks test. The mean and Standard Deviation will be reported for normally distributed data. For data not distributed normally, the median and inter quartile ranges of the data will be reported. Independent samples t-test will be used for between-group comparison (normal distribution). The Mann-Whitney test will be used for non-normal data.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levobupivacaine arm<br>Patients will receive a single injection of 10 mL of 0.5% (5 mg/mL) levobupivacaine into the common extensor origin. | Drug: Liposomal bupivacaine<br>* Patient will receive a single injection of a local anesthetic into the common extensor origin.<br>|
| Experimental: Liposomal Bupivacaine arm<br>Patients will receive a single injection of 10 mL (133mg) of liposomal bupivacaine into the common extensor origin. | Drug: Liposomal bupivacaine<br>* Patient will receive a single injection of a local anesthetic into the common extensor origin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain | pain at rest reported by patient on a Visual Analogue Scale (VAS), scale 0-100, higher value indicating worse outcome | 1 week | 
| Pain | pain at rest reported by patient on a Visual Analogue Scale (VAS), scale 0-100, higher value indicating worse outcome | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain | pain during grip reported by patient on Visual Analogue Scale (VAS), | 1 week | 
| Pain | pain during grip reported by patient on Visual Analogue Scale (VAS), scale 0-100, higher value indicating worse outcome | 1 month | 
| Disability | Patient reported outcome measure Disabilities of the Arm, Shoulder and Hand, scale 0-100, higher value indicating worse outcome | 1 week | 
| Disability | Patient reported outcome measure Disabilities of the Arm, Shoulder and Hand, scale 0-100, higher value indicating worse outcome | 1 month | 
| Disability | Patient reported outcome measure Oxford Elbow Score, scale 0-100, lower value indicating worse outcome | 1 week | 
| Disability | Patient reported outcome measure Oxford Elbow Score, scale 0-100, lower value indicating worse outcome | 1 month | 
| Disability | total number of days of work lost due to epicondylalgia | 1 week | 
| Disability | total number of days of work lost due to epicondylalgia | 1 month | 
| Pain | reduction in the amount of each pain medication taken | 1 week | 
| Pain | reduction in the amount of each pain medication taken | 1 month |