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Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty

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ClinicalTrials.gov Identifier: NCT02713178
Recruitment Status : Recruiting
First Posted : March 18, 2016
Last Update Posted : May 1, 2017
Information provided by (Responsible Party):
Pacira Pharmaceuticals, Inc

Brief Summary:
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in approximately 300 adult subjects undergoing primary unilateral TKA under general or spinal anesthesia.

Condition or disease Intervention/treatment Phase
Pain Drug: bupivacaine liposome injectable suspension Drug: Placebo Phase 3

Detailed Description:

On Day 0, eligible subjects will be randomized in a 1:1:1 ratio to receive a single dose of either EXPAREL 133 mg in 10 mL expanded in volume with 10 mL of normal saline for a total volume of 20 mL (Group 1); EXPAREL 266 mg in 20 mL (Group 2); or placebo 20 mL (Group 3). Study drug (EXPAREL or placebo) will be administered in a blinded manner via an ultrasound guided single-dose femoral nerve block at least 1 hour prior to surgery. Prior to placement of the prosthesis, 8 mL of bupivacaine hydrochloride (HCl) (0.5%) diluted with 8 mL of normal saline will be administered by the surgeon as a periarticular infiltration to the posterior capsule (8 mL medially and 8 mL laterally).

Postsurgical assessments will include pain intensity scores using a 10-cm visual analog scale (VAS); total postsurgical opioid consumption; overall benefit of analgesia score (OBAS) questionnaire; subject satisfaction with overall analgesia using a 5-point Likert scale; neurological assessment; sensory function assessment; motor function assessment; the study physical therapy assessments (ie, timed walk, timed up and go, and stair climbing tests); discharge readiness; unscheduled phone calls or office visits related to pain; 12-lead ECGs; vital sign measurements; and clinical laboratory tests. Adverse events will be recorded from the time the informed consent form (ICF) is signed through postsurgical Day 29.

Follow-up visits will be scheduled for all subjects on postsurgical Days 6 and 10. A follow-up phone call will be made on postsurgical Day 29.

Pharmacokinetic (PK) parameters will be estimated from plasma bupivacaine measurements using non-compartmental analysis based on the sampling schedule of baseline (prior to the nerve block) through postsurgical Day 10.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL for Postsurgical Analgesia in Subjects Undergoing Total Knee Arthroplasty
Study Start Date : March 2016
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: EXPAREL 133 mg
Single dose of 133 mg (10 mL) EXPAREL (bupivacaine liposome injectable suspension) expanded in volume with 10 mL of normal saline for a total volume of 20 mL.
Drug: bupivacaine liposome injectable suspension
bupivacaine liposome injectable suspension 133 mg expanded with normal saline to 20 mL or 266 mg in 20 mL
Other Name: EXPAREL
Active Comparator: EXPAREL 266 mg
Single dose of 266 mg (20 mL) EXPAREL (bupivacaine liposome injectable suspension).
Drug: bupivacaine liposome injectable suspension
bupivacaine liposome injectable suspension 133 mg expanded with normal saline to 20 mL or 266 mg in 20 mL
Other Name: EXPAREL
Placebo Comparator: Placebo
Normal saline (20 mL).
Drug: Placebo
Normal saline.
Other Name: Normal saline

Primary Outcome Measures :
  1. Area under the curve (AUC) of the VAS pain intensity scores [ Time Frame: Through 72 hours ]

Secondary Outcome Measures :
  1. Total postsurgical opioid consumption (in IV morphine equivalents) [ Time Frame: Through 72 hours ]
  2. Percentage of opioid-free subjects [ Time Frame: Through 72 hours ]
  3. Time to first opioid rescue [ Time Frame: Through 72 hours ]

Other Outcome Measures:
  1. Incidence of treatment-emergent adverse events and serious adverse events [ Time Frame: Through postsurgical Day 29 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female, at least 18 years of age at screening.
  2. Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
  3. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
  4. Female subject 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.
  5. Able to demonstrate sensory function by exhibiting sensitivity to cold, pinprick, and light touch.
  6. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

Exclusion Criteria:

  1. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
  2. Planned concurrent surgical procedure (e.g., bilateral TKA).
  3. 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).
  4. Previous open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
  5. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.
  6. Contraindication to any one of the following: bupivacaine, oxycodone, morphine, or hydromorphone.
  7. 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.
  8. 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.
  9. Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
  10. Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration.
  11. History of impaired kidney function, poorly controlled chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.
  12. Impaired kidney function (e.g., serum creatinine level >2 mg/dL [176.8 µmol/L] or blood urea nitrogen level >50 mg/dL [17.9 mmol/L]) or impaired liver function (e.g., serum aspartate aminotransferase [AST] level >3 times the upper limit of normal [ULN] or serum alanine aminotransferase [ALT] level >3 times the ULN.)
  13. Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
  14. Any chronic neuromuscular deficit effecting the peripheral nerves or muscles of the surgical extremity.
  15. Any chronic condition or disease that would compromise neurological or vascular assessments.
  16. Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
  17. Suspected or known history of drug or alcohol abuse within the previous year.
  18. Body weight <50 kg (110 pounds) or a body mass index >44 kg/m2.
  19. Previous participation in an EXPAREL study.
  20. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02713178

Contact: Hassan Danesi 973-451-4047 Hassan.Danesi@pacira.com

United States, Alabama
Brookwood Medical Center Recruiting
Birmingham, Alabama, United States, 35209
Contact: Larry Smith    205-271-6507    lsmith@aoc-research.com   
Principal Investigator: Robert Sorrell, MD         
Horizon Research Group, Inc Recruiting
Mobile, Alabama, United States, 36608
Contact: Elizabeth Hess    251-410-3705    lhess@horizonresearch.us   
Principal Investigator: Robert Calin, MD         
Helen Keller Hospital Recruiting
Sheffield, Alabama, United States, 35660
Contact: Christy Puckett    256-386-4001    puckchristy@comcast.net   
Principal Investigator: Timothy Melson, MD         
United States, Colorado
Denver Metro Orthopedics Not yet recruiting
Englewood, Colorado, United States, 80113
Contact: Hannah Olds    303-789-3000    hannah.olds@colorado.edu   
Principal Investigator: John Schwappach, MD         
United States, Florida
Shrock Orthopedic Research Not yet recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Natalie Shrock    954-626-3743    natalie@shrockresearch.com   
Principal Investigator: Kevin Shrock, MD         
Jackson Memorial Hospital/University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Margarita Nieto Moreno       m.nieto@med.miami.edu   
Contact: Alessandro Colantuono    305-585-7677      
Principal Investigator: Keith Candiotti, MD         
Pensacola Research Associates Recruiting
Pensacola, Florida, United States, 32504
Contact: Amanda Satterwhite    850-477-7900 ext 2003    a.satterwhite@pensacolaresearch.com   
Contact: Donna Lawson    850-477-7900 ext 2105    d.lawson@pensacolaresearch.com   
Principal Investigator: E J Dabezies, Jr., MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ashish Bhandari    617-732-9816    abhandari1@partners.org   
Principal Investigator: Srdjan Nedeljkovic, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Ashish Bhandari    617-732-9816    abhandari1@partners.org   
Principal Investigator: Srdjan Nedeljkovic, MD         
United States, New York
Stony Brook Medicine Recruiting
Stony Brook, New York, United States, 11794
Contact: Sabeen Rizwan    631-638-1214    sabeen.rizwan@stonybrookmedicine.edu   
Principal Investigator: Syed Azim, MD         
Montefiore Medical Center Recruiting
The Bronx, New York, United States, 10467
Contact: Singh Nair    718-920-5932    sinair@montefiore.edu   
Principal Investigator: Boleslav Kosharskyy, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Raleigh-Durham, North Carolina, United States, 27710
Contact: Alicia Pucci       alicia.pucci@duke.edu   
Contact: Renee Visaya    919-668-2437    renee.visaya@duke.edu   
Principal Investigator: Jeffery Gadsden, MD         
United States, Pennsylvania
Indiana Regional Medical Center Recruiting
Indiana, Pennsylvania, United States, 15701
Contact: Sarah Boyer    724-349-0520    sboyer@antria.org   
Principal Investigator: David Bizousky, MD         
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Jennifer Lessin, BA RN CCRC    215-955-5804    jennifer.lessin@jefferson.edu   
Contact: Robert Machinski    610-348-3537    robert.machinski@jefferson.edu   
Principal Investigator: Eugene R Viscusi, MD         
United States, Texas
Hermann Drive Surgical Hospital Recruiting
Houston, Texas, United States, 77004
Contact: Lauren Howard    281-770-5752    lauren@minkowitzmd.com   
Principal Investigator: David Leiman, MD         
Westside Surgical Hospital Recruiting
Houston, Texas, United States, 77027
Contact: Sandra Bailon    713-480-3028    sandra@minkowitzmd.com   
Contact: Pam Lindley    832-567-2273    pam@minkowitzmd.com   
Principal Investigator: Harold Minkowitz, MD         
United States, Virginia
Southampton Orthopaedics Sports Medicine Recruiting
Franklin, Virginia, United States
Contact: Vishaili Patel    267-968-5239    research@summitcr.com   
Principal Investigator: Manish Patel, MD         
Ziekenhuis Oost-Limburg Recruiting
Genk, Belgium
Contact: Monika Golebiewski    491633123175    monica.golebiewski84@gmail.com   
Contact: Marijke Cipers       marijke.cipers@zol.be   
Principal Investigator: Sam Van Boxstael, MD         
Aarhus University Hospital Recruiting
Aarhus C, Denmark
Contact: Siska Bjørn    4560651087    siska.bjoern@post.au.dk   
Principal Investigator: Thomas Fichtner Bendtsen, MD         
Regionshospital Silkeborg Not yet recruiting
Silkeborg, Denmark
Contact: Jens Rolighed Larsen    4530512492    jens.rolighed@clin.au.dk   
Principal Investigator: Jens Rolighed Larsen, MD         
Sponsors and Collaborators
Pacira Pharmaceuticals, Inc
Study Director: James B Jones, MD, PharmD Pacira Pharmaceuticals, Inc

Responsible Party: Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT02713178     History of Changes
Other Study ID Numbers: 402-C-326
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: May 1, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Anesthetics, Local
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents