Single Shot Liposomal Bupivicaine in Rotator Cuff Surgery

A Prospective Randomized Controlled Trial Examining the Effectiveness of a Single Shot of Liposomal Bupivicaine for Reducing Post-operative Pain and Narcotic Use in Outpatient Rotator Cuff Surgery

This document is a protocol for a human research study. This study is to be conducted according to United States standards of Good Clinical Practice in accordance with applicable Federal regulations and institutional research policies and procedures.

Liposomal bupivacaine (LB) has been shown to decrease post-operative pain and narcotic use when administered perioperatively as a local injection during arthroplasty procedures. Studies have also demonstrated that LB used in conjunction with dexamethasone may increase the duration of effectiveness of LB. This study seeks to evaluate if there is a difference in post-operative pain and narcotic use when LB is administered in an interscalene block during outpatient rotator cuff repair surgery. Furthermore, this study aims to determine if the addition of dexamethasone with LB results in a prolonged decrease in post-operative pain and a reduction in narcotic use.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Rotator Cuff Tear
• Intervention / Treatment: Drug: Dexamethasone; Drug: liposomal bupivicaine

Detailed Description

Outpatient surgery has become the gold standard for arthroscopic rotator cuff repair. Innovations in pain management with regional anesthesia and multimodal techniques have greatly contributed to this transition over the past several decades. Despite overall improvements, uncontrolled postoperative pain leads to prolonged ambulatory stays, increased patient dissatisfaction, unexpected admissions to the hospital or visits to the Emergency Room after surgery, and a greater incidence of complications. Furthermore, in the wake of the "opioid epidemic", concerns with narcotic consumption and addiction have become heightened with regulations and laws recently enacted making prescribing and managing postoperative pain ever more difficult.

Interscalene nerve blockade for shoulder procedures has become an increasingly common technique to provide perioperative pain control with good efficacy, low complication rates and reduced narcotic consumption. While the utilization of ultrasound to help administer the block has aided in the accuracy providing a more consistent analgesic effect, its overall short duration (12-24 hours) remains one of the major limitations of this technique. Modalities to prolong its effect have included use of indwelling catheters and the addition of perineural dexamethasone.

Recently, liposomal bupivacaine (LB) (Exparel) was approved for single shot interscalene administration by the FDA. This medication has been purported to provide up to 72 hours of extended release of bupivacaine via its multivesicular and honeycomb-like structure that predictably breaks down resulting in a slow and sustained release of the medication.9 Although numerous studies have been conducted and several meta-analyses performed looking at the overall efficacy of local injections of LB for operative procedures in an inpatient setting, no study to date has independently assessed its efficacy in the new perineural indication for outpatient shoulder surgery. Furthermore, no study to date has compared the use of LB to the use of LB with dexamethasone in a perineural indication to see if the duration of efficacy is further prolonged with the addition of dexamethasone. All existing literature is in regard to use of liposomal bupivacaine injected locally within the surgical site. This will be the first study to examine the perineural use of LB for outpatient shoulder surgery, and to determine if there is a prolonged decrease in pain and a decrease in narcotic consumption with the use of LB with dexamethasone when delivered as an interscalene block in an ambulatory setting.

Utilizing a prospective randomized controlled trial, this study seeks to evaluate if there is a difference in post-operative pain and narcotic use when LB is administered in an interscalene block during outpatient rotator cuff repair surgery. Furthermore, this study aims to determine if the addition of dexamethasone with LB results in a prolonged decrease in post-operative pain and an overall reduction in narcotic use.

Primary Aims & Objective

Aim 1a: To determine if the use of LB in an interscalene block decreases patient-reported post-operative visual analogue pain scale (VAS) in patients undergoing outpatient rotator cuff surgery

Hypothesis: There will be a decrease in the visual analogue pain scale for up to 72 hours post-operatively among participants who receive LB or LB plus dexamethasone, as compared to the control group (bupivacaine plus dexamethasone).

Objective: Utilizing a prospective randomized controlled trial, post-operative patient-reported VAS pain (on a scale of 1-10) will be collected 3 times per day (every 8 hours) for 5 post-operative days (PODs), corresponding to a total of 120 hours after surgery. For each 24-hour period (corresponding to each POD), the pain scores will be averaged and compared between the three treatment groups (control, LB, and LB plus dexamethasone) for each of the 5 PODs.

Aim 1b: To determine if the use of LB plus dexamethasone in an interscalene block decreases patient-reported post-operative VAS pain for a longer duration than the LB or the control group (bupivacaine plus dexamethasone) in patients undergoing outpatient rotator cuff surgery

Hypothesis: There will be a decrease in visual analogue pain scale for greater than 72 hours post-operatively among participants who receive LB plus dexamethasone, as compared to the LB and the control group (bupivacaine plus dexamethasone).

Objective: Utilizing a prospective randomized controlled trial, post-operative patient-reported visual analogue pain scale (on a scale of 1-10) will be collected 3 times per day (every 8 hours) for 5 post-operative days (PODs), corresponding to a total of 120 hours after surgery. For each 24-hour period (corresponding to each POD), the pain scores will be averaged and compared between the three treatment groups (control, LB, and LB plus dexamethasone) for each of the 5 PODs.

Secondary Aims & Objectives

Aim 2a: To determine if there is a difference in time at which post-operative narcotics are first used among three groups receiving different interscalene blocks (LB plus dexamethasone, LB, and control) in patients undergoing outpatient rotator cuff surgery.

Hypothesis: Narcotic use will begin at a later time among those receiving LB plus dexamethasone, as compared to the LB and the control group (bupivacaine plus dexamethasone).

Objective: Utilizing a prospective randomized controlled trial, narcotic use will be collected at 8-hour increments for a total of 5 post-operative days (PODs), corresponding to a period of 120 hours post-surgery. The 8-hour time period during which a participant first begins using a narcotic will be recorded and compared between three treatment groups (control, LB, and LB plus dexamethasone).

Aim 2b: To determine if there is a difference in patient-reported post-operative narcotic use (measured in morphine equivalents) among three groups receiving different interscalene blocks (LB plus dexamethasone, LB, and control) in patients undergoing outpatient rotator cuff surgery.

Hypothesis: There will be a decrease in cumulative narcotic use (measured in morphine equivalents) among participants who receive LB plus dexamethasone, as compared to the LB and the control group (bupivacaine plus dexamethasone).

Objective: Utilizing a prospective randomized controlled trial, post-operative patient-reported narcotic use (measured by the number of tablets ingested and converted to morphine equivalents) will be collected 3 times per day at 8-hour increments for a total of 5 post-operative days (PODs), corresponding to a total of 120 hours after surgery. For each 24-hour period (corresponding to each POD), narcotic use will be tabulated and compared between three treatment groups (control, LB, and LB plus dexamethasone). Furthermore, cumulative narcotic use during the 5-day (120 hour) study period will be calculated and compared between three treatment groups (control, LB, and LB plus dexamethasone).

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 and older
• Primary diagnosis of rotator cuff tear
• Able to provide informed consent
• Is willing and able to accept text messages

Exclusion Criteria:

• Known allergies to the study medications.
• Known narcotic or alcohol abuse (< 3 months)
• Revision rotator cuff surgery
• Contraindication to regional anesthesia
• Current narcotic regimen or contract with pain management specialist

• Diagnosed with any of the following co-morbidities:

  • Pre-existing coagulation disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control/Bupivicaine +DMSO; Group 1 will serve as the control and receive the standard injection consisting 30 ml of 0.5% bupivacaine and 0.4ml (4 mg) of dexamethasone.	Drug: Dexamethasone; steroid that will be used in control as well as in group 3 to see if effect with liposomal bupivicaine is prolonged as has been shown with standard bupivicaine.
Active Comparator: Liposomal bupivicaine; Group 2 will receive a block with 15ml 0.5% bupivacaine and 10ml (133mg) of liposomal bupivicaine (Exparel) and 5.4ml of Normal Saline	Drug: liposomal bupivicaine; The medication administered in the interscalene block is the intervention in this study. There are three different types of interscalene blocks that will be administered in order to compare the independent effectiveness of LB with the effectiveness of LB plus dexamethasone. Study participants will be randomized into one of three groups. The treatment groups are listed below: Group 1 (Control): 30 ml of 0.5% bupivacaine and 0.4ml (4 mg) of dexamethasone Group 2: 15ml 0.5% bupivacaine and 10ml (133mg) of LB (Exparel) and 5.4ml normal saline Group 3: 5ml 0.5% bupivacaine and 10ml LB (Exparel) and 0.4ml (4 mg) dexamethasone and 5ml normal saline; Other Names: Exparel
Active Comparator: Liposomal Bupivicaine +DMSO; Group 3 will receive 15ml of 0.5% bupivicaine and 10ml (133mg) of Liposomal Bupivicaine (Exparel) and 0.4ml (4mg) dexamethasone and 5ml normal saline	Drug: Dexamethasone; steroid that will be used in control as well as in group 3 to see if effect with liposomal bupivicaine is prolonged as has been shown with standard bupivicaine.; Drug: liposomal bupivicaine; The medication administered in the interscalene block is the intervention in this study. There are three different types of interscalene blocks that will be administered in order to compare the independent effectiveness of LB with the effectiveness of LB plus dexamethasone. Study participants will be randomized into one of three groups. The treatment groups are listed below: Group 1 (Control): 30 ml of 0.5% bupivacaine and 0.4ml (4 mg) of dexamethasone Group 2: 15ml 0.5% bupivacaine and 10ml (133mg) of LB (Exparel) and 5.4ml normal saline Group 3: 5ml 0.5% bupivacaine and 10ml LB (Exparel) and 0.4ml (4 mg) dexamethasone and 5ml normal saline; Other Names: Exparel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Postoperative Pain: VAS	Patient-reported post-operative VAS pain (on a scale of 0-10 with zero implying no pain and 10 indicating severe pain), measured post operatively, in 8-hour increments, for a total of 96 hours post-surgery, Patients will be prompted via text message to provide VAS pain every 8 hours. If a response text message is not received, a phone call will be made to obtain the information. Patients who do not have a smart phone will receive a phone call or keep a personal log of VAS pain.	4 days post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Post Operative Opioid Use	Patient-reported post-operative opioid use (converted to morphine equivalents), collected post operatively, in 8-hour increments, for a total of 96 hours post-surgery Patients will be prompted via text message to provide the amount of narcotics (number of pills converted to morphine equivalents) taken over the course of the previous 8 hours. If a response text message is not received, a phone call will be made to obtain the information. Patients who do not have a smart phone will receive a phone call or keep a personal log of narcotic use.	4 days post procedure

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: brian badman, MD, Indiana University

Publications and helpful links

General Publications

• Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012 Oct;19(5):530-6. doi: 10.1016/j.knee.2011.12.004. Epub 2012 Jan 28.
• Cao X, Pan F. Comparison of liposomal bupivacaine infiltration versus interscalene nerve block for pain control in total shoulder arthroplasty: A meta-analysis of randomized control trails. Medicine (Baltimore). 2017 Sep;96(39):e8079. doi: 10.1097/MD.0000000000008079.
• Surdam JW, Licini DJ, Baynes NT, Arce BR. The use of exparel (liposomal bupivacaine) to manage postoperative pain in unilateral total knee arthroplasty patients. J Arthroplasty. 2015 Feb;30(2):325-9. doi: 10.1016/j.arth.2014.09.004. Epub 2014 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2018
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): January 22, 2020

Study Registration Dates

• First Submitted: January 27, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: liposomal bupivicaine; interscalene block
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Wounds and Injuries; Rupture; Shoulder Injuries; Tendon Injuries; Pain, Postoperative; Rotator Cuff Injuries; Physiological Effects of Drugs; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anesthetics, Local; Dexamethasone; Bupivacaine
• Other Study ID Numbers: 1806933448

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plans to share

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.: No