Comparing Post-Op Narcotic Usage in Patients Receiving Periarticular Exparel vs. Standard Periarticular Joint Inj

• Sponsor: University of California, Irvine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02682498
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study seeks to determine whether a new sustained-release local anesthetic solution (Exparel - Liposomal Bupivacaine) injected into the soft tissues around the joint after surgery will decrease opioid consumption and adverse events in opioid-tolerant patients presenting for total knee arthroplasty. The research hypothesis is that the Exparel (study) group will use less opioid in the first 48 hours post-operatively than the control group.

Condition or Disease	Intervention/Treatment	Phase
Arthroplasty, Replacement, Knee	Drug: (Bupivacaine Liposome Injectable Suspension); Drug: Standard Preparation	Phase 4

Detailed Description

Opioids have been prescribed with increasing frequency for non-acute, non-cancer pain in the last 15 years. Because of this, opioid tolerance in the general population has grown markedly, and opioid tolerant patients can be especially difficult to manage in the perioperative period. In general, they require much higher doses of opioids to obtain similar levels of pain-control compared to opioid-naïve patients and are susceptible to respiratory depression and other adverse events. This study seeks to determine whether a new sustained-release local anesthetic solution (Exparel - Liposomal Bupivacaine) injected into the soft tissues around the joint after surgery will decrease opioid consumption and adverse events in opioid-tolerant patients presenting for total knee arthroplasty.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double Blind, Randomized Clinical Trial Comparing Postoperative Narcotic Usage in Patients Receiving Periarticular Liposomal Bupivicaine vs. Those Patients Receiving Standard Periarticular Joint Injections
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: EXPAREL® Bupivacaine Liposome Suspension Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours.	Drug: (Bupivacaine Liposome Injectable Suspension); Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.; Other Names: EXPAREL®
Active Comparator: Standard periarticular joint injection A standard joint injection of 100ml (Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml) will be injected into the soft tissues around the joint after surgery.	Drug: Standard Preparation; A standard joint injection of 100ml (Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml) will be injected into the soft tissues around the joint after surgery.; Other Names: Standard Periarticular Joint Injection

Outcome Measures

Primary Outcome Measures

1. 48 Hour Post-surgical Opioid Use [48 hours]

   A comparison of group means between the control group and study group with regards to 48 hour opioid use.

Secondary Outcome Measures

1. Recovery Room Opioid Use [Up to 48 hours]

   Post anesthesia care unit (recovery room) opioid use in total mg morphine IV equivalent in comparison of standard knee injection post-operatively.

2. Average Daily Opioid Use During Admission [Up to 48 hours]

   Opioid use will be monitored daily from the time of admission in comparison of standard knee injection post-operatively.

3. Average Daily Patient Pain Score [Up to 48 hours]

   Examining the average daily patient pain score in comparison of standard knee injection post-operatively. The measure is the Visual-Analog-Scale (VAS) for subjective pain reporting. The minimum 0 (no pain) and the maximum is 10 (worst pain imagineable). There is only one measure in the scale (i.e. there are no subscales). Lower scores on the VAS scale equate to less pain and are therefore desirable.

4. Post-operative Complications [Up to 1 month]

   Examining the post-operative complication in comparison of standard knee injection post-operatively.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and Females age 18+ years old having total knee arthroplasty at UCI

• Meet at least one of the following criteria "opioid tolerant":

• Taking 50mg oral morphine equivalent or more per day

• On long-acting opioids (fentanyl pathc, oxycontin, methadone, etc.)

• Being followed by a chronic pain physician

• All subjects must be free of renal or hepatic dysfunction; defined as:

• Glomerular filtration rate >60 mL/min/1.73m^2

• AST & ALT <150, total bilirubin <1.0, INR <1.3 (if not taking anticoagulants)

• No active hepatitis, no jaundice

Control group- received standard periarticular injection Research group- receives Exparel injection

Exclusion Criteria:

• Allergy to local Anesthetic

• Pregnancy

• Nursing mothers

• Children<18 years of age

• Renal impairment (GFR<60 mL/min/1.73 m^2

• Hepatic impairment (active hepatitis, elevated AST or ALT, jaundice)

• Any history of ventricular arrhythmia or supraventricular tachycardia, or myocardial infarction within the last six months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Irvine Medical Center	Orange	California	United States	92868

Sponsors and Collaborators

• University of California, Irvine

Investigators

• Principal Investigator: Joseph Rinehart, M.D., University of California, Irvine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bergese SD, Ramamoorthy S, Patou G, Bramlett K, Gorfine SR, Candiotti KA. Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia. J Pain Res. 2012;5:107-16. doi: 10.2147/JPR.S30861. Epub 2012 May 1.
• Candiotti K. Liposomal bupivacaine: an innovative nonopioid local analgesic for the management of postsurgical pain. Pharmacotherapy. 2012 Sep;32(9 Suppl):19S-26S. doi: 10.1002/j.1875-9114.2012.01183.x.
• Chahar P, Cummings KC 3rd. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012;5:257-64. doi: 10.2147/JPR.S27894. Epub 2012 Aug 14.
• Chen Y, Zhang Y, Zhu YL, Fu PL. Efficacy and safety of an intra-operative intra-articular magnesium/ropivacaine injection for pain control following total knee arthroplasty. J Int Med Res. 2009 Nov-Dec;37(6):1733-41. Retraction in: J Int Med Res. 2012;40(5):2031. Corrected and republished in: J Int Med Res. 2012;40(5):2032-40.
• Cohen SM. Extended pain relief trial utilizing infiltration of Exparel(®), a long-acting multivesicular liposome formulation of bupivacaine: a Phase IV health economic trial in adult patients undergoing open colectomy. J Pain Res. 2012;5:567-72. doi: 10.2147/JPR.S38621. Epub 2012 Nov 20.
• Fu P, Wu Y, Wu H, Li X, Qian Q, Zhu Y. Efficacy of intra-articular cocktail analgesic injection in total knee arthroplasty - a randomized controlled trial. Knee. 2009 Aug;16(4):280-4. doi: 10.1016/j.knee.2008.12.012. Epub 2009 Mar 18.
• Grant GJ, Barenholz Y, Bolotin EM, Bansinath M, Turndorf H, Piskoun B, Davidson EM. A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. Anesthesiology. 2004 Jul;101(1):133-7.
• Grant GJ, Piskoun B, Bansinath M. Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice. Clin Exp Pharmacol Physiol. 2003 Dec;30(12):966-8.
• Huxtable CA, Roberts LJ, Somogyi AA, MacIntyre PE. Acute pain management in opioid-tolerant patients: a growing challenge. Anaesth Intensive Care. 2011 Sep;39(5):804-23. Review.
• Patanwala AE, Jarzyna DL, Miller MD, Erstad BL. Comparison of opioid requirements and analgesic response in opioid-tolerant versus opioid-naïve patients after total knee arthroplasty. Pharmacotherapy. 2008 Dec;28(12):1453-60. doi: 10.1592/phco.28.12.1453.
• Richard BM, Newton P, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG. The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs. J Drug Deliv. 2012;2012:962101. doi: 10.1155/2012/962101. Epub 2012 Jan 17.
• Richard BM, Rickert DE, Newton PE, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG. Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison. J Drug Deliv. 2011;2011:467429. doi: 10.1155/2011/467429. Epub 2011 Oct 5.
• Urban MK, Ya Deau JT, Wukovits B, Lipnitsky JY. Ketamine as an adjunct to postoperative pain management in opioid tolerant patients after spinal fusions: a prospective randomized trial. HSS J. 2008 Feb;4(1):62-5. doi: 10.1007/s11420-007-9069-9. Epub 2007 Dec 19.
• Zywiel MG, Stroh DA, Lee SY, Bonutti PM, Mont MA. Chronic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am. 2011 Nov 2;93(21):1988-93. doi: 10.2106/JBJS.J.01473.

• Responsible Party: Joseph Brian Rinehart, Assistant Professor of Clinical Anesthesiology, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT02682498
• Other Study ID Numbers: UCIANES08
• First Posted: Feb 15, 2016
• Last Update Posted: Jul 7, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Joseph Brian Rinehart, Assistant Professor of Clinical Anesthesiology, University of California, Irvine: Knee Arthroplasty, Total; Liposomal Bupivicaine
• Additional relevant MeSH terms: Bupivacaine

Study Results

Participant Flow

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
Period Title: Overall Study
STARTED	18	20
COMPLETED	18	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection	Total
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.	Total of all reporting groups
Overall Participants	20	18	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.14 (10.18)	60 (12.83)	60 (11)
Sex: Female, Male (Count of Participants)
Female	9 45%	12 66.7%	21 55.3%
Male	11 55%	6 33.3%	17 44.7%

Outcome Measures

1. Primary Outcome

Title	48 Hour Post-surgical Opioid Use
Description	A comparison of group means between the control group and study group with regards to 48 hour opioid use.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
Measure Participants	20	18
Mean (Standard Deviation) [morphine equivalents]	5.32 (1.72)	5.07 (2.05)

2. Secondary Outcome

Title	Recovery Room Opioid Use
Description	Post anesthesia care unit (recovery room) opioid use in total mg morphine IV equivalent in comparison of standard knee injection post-operatively.
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
Measure Participants	20	18
Median (Inter-Quartile Range) [Total morphine equivalents]	5	5

3. Secondary Outcome

Title	Average Daily Opioid Use During Admission
Description	Opioid use will be monitored daily from the time of admission in comparison of standard knee injection post-operatively.
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
Measure Participants	20	18
Mean (Inter-Quartile Range) [Total Morphine Equivalents]	100	103

4. Secondary Outcome

Title	Average Daily Patient Pain Score
Description	Examining the average daily patient pain score in comparison of standard knee injection post-operatively. The measure is the Visual-Analog-Scale (VAS) for subjective pain reporting. The minimum 0 (no pain) and the maximum is 10 (worst pain imagineable). There is only one measure in the scale (i.e. there are no subscales). Lower scores on the VAS scale equate to less pain and are therefore desirable.
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml (Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml) will be injected into the soft tissues around the joint after surgery.
Measure Participants	20	18
Mean (Inter-Quartile Range) [Visual Analog Scale Rating]	4.75	5.75

5. Secondary Outcome

Title	Post-operative Complications
Description	Examining the post-operative complication in comparison of standard knee injection post-operatively.
Time Frame	Up to 1 month

Outcome Measure Data

Analysis Population Description

The vast majority of the patients had been discharged by 72 hours post-op, making this outcome low-powered and not useful. Because of this we used the 48 hour pain measurement.

Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension	Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.	A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
Measure Participants	18	20
Number [complications]	0	0

Adverse Events

Time Frame	10/24/13-8/18/15
Arm/Group Title	EXPAREL® Bupivacaine Liposome Suspension		Standard Periarticular Joint Injection
Arm/Group Description	Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-Liposomal Bupivicaine will be administered at the end of the surgery. A new sustained-release local anesthetic solution (Bupivacaine Liposome Injectable Suspension) will be injected into the soft tissues around the join after surgery. Exparel is a novel-composition of bupivacine in which the drug is dissolved into liposomes which release it slowly over a period of 72 hours. (Bupivacaine Liposome Injectable Suspension): Instead of injecting the standard joint injection for a case of total knee arthroplasty, Exparel-lipsomal bupivacaine will be administered at the end of the surgery.		A standard joint injection of 100ml which contains Clonidine 80 mcg, Epinephrine 0.5mg, Ketorolac 30mg, Ropivacaine 246.25mg, and Sodium Chloride 0.9% 48.45 ml will be injected into the soft tissues around the joint after surgery.
All Cause Mortality
	EXPAREL® Bupivacaine Liposome Suspension		Standard Periarticular Joint Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	EXPAREL® Bupivacaine Liposome Suspension		Standard Periarticular Joint Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	EXPAREL® Bupivacaine Liposome Suspension		Standard Periarticular Joint Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.