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

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

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

Study Overview

• Status: Unknown
• Conditions: Lateral Epicondylitis; Tennis Elbow
• Intervention / Treatment: Drug: Liposomal bupivacaine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joona Ikonen, MD; Phone Number: +358 (0)2 3130298; Email: joona.ikonen@tyks.fi
• Study Contact Backup: Name: Markus Pääkkönen, PhD, Docent; Phone Number: +358 (0)2 313 0000; Email: markus.paakkonen@tyks.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Levobupivacaine arm; Patients will receive a single injection of 10 mL of 0.5% (5 mg/mL) levobupivacaine into the common extensor origin.	Drug: Liposomal bupivacaine; Patient will receive a single injection of a local anesthetic into the common extensor origin.
EXPERIMENTAL: Liposomal Bupivacaine arm; Patients will receive a single injection of 10 mL (133mg) of liposomal bupivacaine into the common extensor origin.	Drug: Liposomal bupivacaine; Patient will receive a single injection of a local anesthetic into the common extensor origin.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Study Director: Markus Pääkkönen, PhD, Docent, Turku University Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (ACTUAL): May 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Arm Injuries; Elbow Tendinopathy; Tennis Elbow; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: TYKS/LeLiBu/1-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes