NCT02682498

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Oct 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2013

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 3, 2016

Completed
12 days until next milestone

First Posted

Study publicly available on registry

February 15, 2016

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

July 7, 2017

Completed
Last Updated

July 7, 2017

Status Verified

July 1, 2017

Enrollment Period

1.7 years

First QC Date

February 3, 2016

Results QC Date

October 31, 2016

Last Update Submit

July 5, 2017

Conditions

Arthroplasty, Replacement, Knee

Keywords

Knee Arthroplasty, TotalLiposomal Bupivicaine

Outcome Measures

Primary Outcomes (1)

  • 48 Hour Post-surgical Opioid Use

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

    48 hours

Secondary Outcomes (4)

  • Recovery Room Opioid Use

    Up to 48 hours

  • Average Daily Opioid Use During Admission

    Up to 48 hours

  • Average Daily Patient Pain Score

    Up to 48 hours

  • Post-operative Complications

    Up to 1 month

Study Arms (2)

EXPAREL® Bupivacaine Liposome Suspension

ACTIVE COMPARATOR

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)

Standard periarticular joint injection

ACTIVE COMPARATOR

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

Interventions

(Bupivacaine Liposome Injectable Suspension)DRUG

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.

Also known as: EXPAREL®
EXPAREL® Bupivacaine Liposome Suspension
Standard PreparationDRUG

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.

Also known as: Standard Periarticular Joint Injection
Standard periarticular joint injection

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Related Publications (14)

  • 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. doi: 10.1177/0310057X1103900505.

    PMID: 21970125BACKGROUND

  • 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.

    PMID: 22048093BACKGROUND

  • Patanwala AE, Jarzyna DL, Miller MD, Erstad BL. Comparison of opioid requirements and analgesic response in opioid-tolerant versus opioid-naive patients after total knee arthroplasty. Pharmacotherapy. 2008 Dec;28(12):1453-60. doi: 10.1592/phco.28.12.1453.

    PMID: 19025426BACKGROUND

  • 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.

    PMID: 18751864BACKGROUND

  • Cohen SM. Extended pain relief trial utilizing infiltration of Exparel((R)), 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.

    PMID: 23204866BACKGROUND

  • 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.

    PMID: 22956491BACKGROUND

  • 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.

    PMID: 22570563BACKGROUND

  • 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. doi: 10.1177/147323000903700609.

    PMID: 20146871BACKGROUND

  • 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.

    PMID: 19299145BACKGROUND

  • Richard BM, Newton P, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG. The Safety of EXPAREL (R) (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.

    PMID: 22363842BACKGROUND

  • 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.

    PMID: 22013534BACKGROUND

  • 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.

    PMID: 23049275BACKGROUND

  • 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. doi: 10.1097/00000542-200407000-00021.

    PMID: 15220782BACKGROUND

  • 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. doi: 10.1111/j.1440-1681.2003.03933.x.

    PMID: 14678238BACKGROUND

MeSH Terms

Interventions

Reference Standards

Intervention Hierarchy (Ancestors)

Weights and MeasuresInvestigative Techniques

Results Point of Contact

Title
Joseph Rinehart
Organization
UC Irvine Health
jrinehar@uci.edu
714-456-5059

Study Officials

  • Joseph Rinehart, M.D.

    University of California, Irvine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Clinical Anesthesiology

Study Record Dates

First Submitted

February 3, 2016

First Posted

February 15, 2016

Study Start

October 1, 2013

Primary Completion

July 1, 2015

Study Completion

August 1, 2015

Last Updated

July 7, 2017

Results First Posted

July 7, 2017

Record last verified: 2017-07

Data Sharing

IPD Sharing
Will not share

Locations

US(1)