Intraoperative Liposomal Bupivacaine Injection in Primary Total Knee Arthroplasty

Prospective Randomized Trial Comparing Intraoperative Liposomal Bupivacaine Injection With Indwelling Femoral Nerve Blockade in Early Postoperative Pain Control for Primary Total Knee Arthroplasty

The purpose of the study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain in primary total knee arthroplasty. The investigators hope to demonstrate equivalency of treatment modalities to provide an alternative to the commonly used treatment of femoral nerve blockade.

Study Overview

• Status: Withdrawn
• Conditions: Osteoarthritis; Osteoarthritis, Knee; Arthritis, Degenerative; Osteoarthrosis; Osteoarthrosis Deformans
• Intervention / Treatment: Drug: Indwelling femoral nerve block; Drug: Bupivacaine Liposome Injection

Detailed Description

Postoperative pain control in total knee arthroplasty is generally managed by a multimodal approach of premedication, epidural and/or peripheral nerve blocks, narcotic medications, and anti-inflammatories. Multiple studies have evaluated the efficacy of anesthetic "cocktails" of various medications for local tissue infiltration to aide in controlling postoperative pain. A recent systematic review supported the use of local anesthetic infiltration in a single intraoperative dose as an adjunct to femoral nerve block in the relief of pain; with combinations of ropivacaine, ketorolac, and adrenaline providing the best results. Several studies noted decreases in opioid consumption and overall pain scores in the perioperative period.

A novel compound, liposomal bupivacaine (EXPAREL®, Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA), has been proposed for use in total knee arthroplasty. To our knowledge, only one randomized controlled trial involving use of this compound in total knee arthroplasty has been published and was performed as a phase two dose ranging trial comparing liposomal bupivacaine to bupivacaine HCl. No statistically significant difference between the two compounds was shown, but a trend towards benefit in short term pain control was shown with EXPAREL 532mg.

Our current pain management regimen utilizes the multimodal approach of neuraxial anesthesia, indwelling femoral nerve catheter, opioids, and anti-inflammatory medications. The regional anesthesia service manages postoperative pain while the indwelling femoral nerve catheter is in place. The epidural is utilized for early postoperative analgesia and thromboprophylaxis. The epidural is discontinued on post-operative day 1 and the femoral nerve catheter is removed by the morning of postoperative day 3. Although femoral nerve catheters provide excellent pain control following TKA, there are associated disadvantages. Most notably there is inherent quadriceps weakness which places the patient at increased fall risk. To reduce the risk of falling, patients must wear a knee immobilizer with ambulation until the catheter is removed and quadriceps function has returned. This may delay the ability to actively participate in physical therapy.

The purpose of our present study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain. The investigators aim to show equivalency between the two treatment modalities. Our hypothesis is that a systematic local infiltration of liposomal bupivacaine provided intraoperatively is equally efficacious as femoral indwelling peripheral nerve blockade in immediate postoperative pain control with more rapid progression with physical therapy.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92134
      • Naval Medical Center San Diego

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 over 18 years old
• Undergoing unilateral primary total knee arthroplasty

Exclusion Criteria:

• Revision total knee arthroplasty
• Bilateral total knee arthroplasty
• Prior allergy or adverse reaction to local anesthetic
• Hepatic dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Femoral Nerve Blockade; Femoral nerve block delivered via indwelling femoral nerve catheter	Drug: Indwelling femoral nerve block; Femoral nerve block delivered via indwelling femoral nerve catheter with 0.125% bupivacaine.
Experimental: Bupivacaine Liposome Injection; Intraoperative intracapsular injection of bupivacaine liposome	Drug: Bupivacaine Liposome Injection; Intraoperative intracapsular injection of 266mg of bupivacaine liposome injection diluted to 60mL with 0.9% normal saline.; Other Names: EXPAREL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Pain Scale	10cm VAS scale completed by the patient at set intervals postoperatively	0-3 months
Oral and Intravenous Opioid Consumption	Oral and intravenous opioid use calculated in terms of morphine equivalents	0-5 days (during hospitalization)
Hospital for Special Surgery (HSS) Knee Scores	Standardized functional clinical score for knee symptoms	0-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay		0-5 days
Distance ambulated with physical therapy		0-5 days (during hospitalization)
Time to straight leg raise with physical therapy	Time to return of quadriceps function	0-5 days (during hospitalization)
Postoperative range of motion	Knee range of motion measure by physical therapy and in clinic	0-3 months
Postoperative complication rate	All intervention related complications for each arm of the study	0-3 months
Plasma bupivacaine concentrations	Plasma levels of bupivacaine monitored throughout hospital stay	0-5 days (during hospitalization)

Collaborators and Investigators

• Sponsor: United States Naval Medical Center, San Diego
• Investigators: Principal Investigator: Patrick B Morrissey, M.D., Naval Medical Center San Diego Department of Orthopadic Surgery

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): October 1, 2015
• Study Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Total Knee Arthroplasty; Liposomal Bupivacaine; Femoral Nerve Blockade
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: NMCSD.2014.0101

Drug and device information, study documents

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