Local Infiltration Analgesia With and Without EXPAREL Following Total Knee Arthroplasty

NCT02713490 | Completed Phase 4 Results

• 1 other identifier: 402-C-331
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 17

Brief Summary

This is a Phase 4, multicenter, randomized, double-blind, controlled trial in approximately 140 adult subjects undergoing primary unilateral TKA under spinal anesthesia with bupivacaine HCl (10-15 mg).

Conditions

Pain

Outcome Measures

Primary Outcomes (2)

• Area Under The Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores From 12 to 48 Hours

  AUC of VAS pain intensity scores from 12 to 48 hours, which represents total pain experienced from 12 to 48 hours. Visual Analog Scale (VAS) is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."

  From 12-48 hours

• Total Postsurgical Opioid Consumption Through 48 Hours

  Total postsurgical opioid consumption (converted to oral morphine equivalents) through 48 hours

  0-48 hours

Secondary Outcomes (3)

• Percentage of Opioid-free Subjects at 48 Hours

  48 hours

• Time to First Opioid Rescue in the First 48 Hours

  48 hours

• Overall Benefit of Analgesia Score at 48 Hours

  48 hours

Study Arms (2)

EXPAREL

ACTIVE COMPARATOR

Single dose of EXPAREL 266 mg in 20 mL admixed with bupivacaine HCl 0.5% in 20 mL and expanded in volume with 80 mL normal saline (total volume of 120 mL).

Drug: EXPAREL

Bupivacaine

ACTIVE COMPARATOR

Bupivacaine HCl 0.5% in 20 mL expanded in volume with 100 mL normal saline (total volume of 120 mL).

Drug: Bupivacaine

Interventions

EXPAREL DRUG

EXPAREL and bupivacaine HCl

Also known as: bupivacaine liposome injectable suspension

EXPAREL

Bupivacaine DRUG

Single dose of bupivacaine HCl 0.5%

Also known as: bupivacaine HCl

Bupivacaine

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 18 years of age at screening.
• Scheduled to undergo primary, unilateral, tricompartmental TKA under spinal anesthesia.
• Primary indication for TKA is degenerative osteoarthritis of the knee.
• American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
• Female subjects must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
• Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

You may not qualify if:

• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
• History of previous prior contralateral TKA or open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
• Planned concurrent surgical procedure (e.g., bilateral TKA).
• Undergoing unicompartmental TKA or revision TKA.
• Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the knee surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery).
• Comorbidity impacting current physical function of Investigator opinion that it may impact postsurgical rehabilitation.
• Allergy, hypersensitivity, or contraindication to any of the study medications (i.e., bupivacaine, pregabalin, acetaminophen/paracetamol, celecoxib, oxycodone, morphine, hydromorphone, or tranexamic acid).
• Use of any of the following medications within the times specified before surgery: long-acting opioid medication or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours.
• Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a subject is taking one of these medications for a reason other than pain control, he or she must be on a stable dose for at least 1 month prior to study drug administration.
• Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
• Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration.
• History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion).
• Have been treated for a deep vein thrombosis, pulmonary embolism, myocardial infarction, or ischemic stroke within the past 6 months (may be extended to 1 year if medically indicated per physician discretion).
• Rheumatoid or inflammatory arthritis or disease.
• Severely impaired renal or hepatic function (e.g., serum creatinine level \>2 mg/dL \[176.8 µmol/L\], blood urea nitrogen level \>50 mg/dL \[17.9 mmol/L\], serum aspartate aminotransferase \[AST\] level \>3 times the upper limit of normal \[ULN\], or serum alanine aminotransferase \[ALT\] level \>3 times the ULN.)

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (17)

Institute for Joint Restoration

Fremont, California, 94538, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33334, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Pinnacle Orthopaedics & Sports

Marietta, Georgia, 30060, United States

Location

Central DuPage Hospital, Northwestern Medicine

Winfield, Illinois, 60190, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Orthopaedic Associates

Towson, Maryland, 21204, United States

Location

NYU Hospital for Joint Disease

New York, New York, 10003, United States

Location

Lenox Hill Hospital/Northwell Health Orthopaedic Institute

New York, New York, 10075, United States

Location

UNC Orthopaedics Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

OrthoCarolina, PA

Charlotte, North Carolina, 28207, United States

Location

Wellington Orthopaedics and Sports Medicine

Cincinnati, Ohio, 45209, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Baylor Medical Center, Plano Orthopedics Sports Medical & Spine Center

Frisco, Texas, 75034, United States

Location

Utah University Orthopedic Center

Salt Lake City, Utah, 84108, United States

Location

Related Publications (2)

• Dysart SH, Barrington JW, Del Gaizo DJ, Sodhi N, Mont MA. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Early Outcomes After Total Knee Arthroplasty: 24-Hour Data From the PILLAR Study. J Arthroplasty. 2019 May;34(5):882-886.e1. doi: 10.1016/j.arth.2018.12.026. Epub 2018 Dec 25.

  PMID: 30799269 DERIVED

• Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial. J Arthroplasty. 2018 Jan;33(1):90-96. doi: 10.1016/j.arth.2017.07.024. Epub 2017 Jul 25.

  PMID: 28802777 DERIVED

MeSH Terms

Conditions

Pain

Interventions

Bupivacaine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Pacira Medical Information
• Organization: Pacira Pharmaceuticals, Inc.

MedInfo@pacira.com

1-855-793-9727

Study Officials

• James B Jones, MD, PharmD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 18, 2016
• Study Start: April 18, 2016
• Primary Completion: February 8, 2017
• Study Completion: February 8, 2017
• Last Updated: December 11, 2020
• Results First Posted: December 11, 2020

Record last verified: 2020-12

Locations

US (17)