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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 : Completed
First Posted : March 18, 2016
Last Update Posted : June 7, 2018
Sponsor:
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)
Actual Enrollment : 232 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
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


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, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Locations
United States, Alabama
Horizon Research Group, Inc
Mobile, Alabama, United States, 36608
United States, Colorado
Denver Metro Orthopedics
Englewood, Colorado, United States, 80113
United States, Florida
Jackson Memorial Hospital/University of Miami
Miami, Florida, United States, 33136
Pensacola Research Associates
Pensacola, Florida, United States, 32504
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02215
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Ohio
Fairview Hospital
Cleveland, Ohio, United States
United States, Pennsylvania
Indiana Regional Medical Center
Indiana, Pennsylvania, United States, 15701
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Chan Soon-Shiong Medical Center
Windber, Pennsylvania, United States, 15963
United States, Texas
Hermann Drive Surgical Hospital
Houston, Texas, United States, 77004
Westside Surgical Hospital
Houston, Texas, United States, 77027
United States, Virginia
Southampton Orthopaedics Sports Medicine
Franklin, Virginia, United States
Belgium
Ziekenhuis Oost-Limburg
Genk, Belgium
Denmark
Aarhus University Hospital
Aarhus C, Denmark
Regionshospital Silkeborg
Silkeborg, Denmark
Sponsors and Collaborators
Pacira Pharmaceuticals, Inc
Investigators
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: June 7, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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