Intraoperative Liposomal Bupivacaine Injection in Primary Total Knee Arthroplasty

Phase 2

Withdrawn

• Conditions: Osteoarthritis, Knee; Arthritis, Degenerative; Osteoarthrosis; Osteoarthrosis Deformans; Osteoarthritis
• Interventions: Drug: Bupivacaine Liposome Injection; Drug: Indwelling femoral nerve block

• Registration Number: NCT02341079
• Lead Sponsor: United States Naval Medical Center, San Diego

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-01-14
• Study First Submitted QC: 2015-01-16
• Study First Posted: 2015-01-19
• Study Start: 2015-03
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-07
• Last Update Posted: 2017-03-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bupivacaine Liposome Injection	Bupivacaine Liposome Injection	Intraoperative intracapsular injection of bupivacaine liposome
Femoral Nerve Blockade	Indwelling femoral nerve block	Femoral nerve block delivered via indwelling femoral nerve catheter

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Naval Medical Center San Diego; 🇺🇸 San Diego, California, United States