Local Infiltration Analgesia With and Without EXPAREL Following Total Knee Arthroplasty

Sponsor
Pacira Pharmaceuticals, Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT02713490
Collaborator
(none)
140
17
2
9.7
8.2
0.8

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

On Day 0, eligible subjects will be randomized 1:1 to two treatment groups. Subjects in Group 1 will receive local infiltration analgesia (LIA) with EXPAREL 266 mg in 20 mL admixed with bupivacaine hydrochloride (HCl) 0.5% in 20 mL and expanded in volume with 80 mL normal saline (total volume of 120 mL). Subjects in Group 2 will receive LIA with bupivacaine HCl 0.5% in 20 mL expanded in volume with 100 mL normal saline (total volume of 120 mL). Investigators will use their usual surgical technique to perform the TKA.

Study drug will be administered using six 20 cc syringes with 22-gauge needles prior to wound closure. Each stick should deliver approximately 1-1.5 cc to the intended area. The tissue should visibly expand with minimal leakage. Study drug should be injected in the prescribed locations based on the areas of highest nerve density.

Infiltration Technique

Prior to cementation

Syringe #1: Posterior capsule (8-10 sticks medial and 8-10 sticks lateral).

Syringe #2: Femur medial and lateral periosteum, posterior periosteum, suprapatellar/quadriceps tendon (20 sticks).

Syringe #3: Tibia fat pad (5 sticks); pes anserinus, medial collateral ligament, and gutter (15 sticks).

Syringe #4: Circumferential periosteum (15-20 sticks).

After cementation

Syringe #5: Midline quadriceps tendon (10 sticks); retinaculum, medial gutter, femoral to tibia (10 sticks).

Syringe #6: Lateral gutter, femoral to tibial (10 sticks); subcutaneous/closure (10 sticks).

In addition to LIA, all study participants will receive a standardized approach for managing postsurgical pain that includes a scheduled multimodal pain regimen including adjunctive analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and rescue analgesics as needed.

Postsurgical clinical assessments will include pain intensity scores using a 10-cm visual analog scale (VAS); overall benefit of analgesia score (OBAS) questionnaire; total postsurgical opioid consumption; physical therapy assessment; nurse's satisfaction with overall analgesia; and discharge readiness. Adverse events (AEs) will be recorded from the time the informed consent form is signed through postsurgical Day 29.

Postsurgical health economic outcome assessments will include hospital length of stay (LOS), use of skilled nursing facility, outpatient physical therapy use, hospital readmissions, and use of other health services following discharge (phone calls related to postsurgical pain, unscheduled visits related to postsurgical pain, and visits to emergency department) through postsurgical Day 29.

A follow-up visit will be scheduled for all subjects on postsurgical Day 14. A follow-up phone call will be made on postsurgical Day 29 to all subjects who received study drug to assess for AEs.

Study Design

Study Type:
Interventional
Actual Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Controlled Trial Comparing Local Infiltration Analgesia With EXPAREL to Local Infiltration Analgesia Without EXPAREL to Manage Postsurgical Pain Following Total Knee Arthroplasty
Study Start Date :
Apr 18, 2016
Actual Primary Completion Date :
Feb 8, 2017
Actual Study Completion Date :
Feb 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: EXPAREL

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
EXPAREL and bupivacaine HCl
Other Names:
  • bupivacaine liposome injectable suspension
  • Active Comparator: Bupivacaine

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

    Drug: Bupivacaine
    Single dose of bupivacaine HCl 0.5%
    Other Names:
  • bupivacaine HCl
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under The Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores From 12 to 48 Hours [From 12-48 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."

    2. Total Postsurgical Opioid Consumption Through 48 Hours [0-48 hours]

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

    Secondary Outcome Measures

    1. Percentage of Opioid-free Subjects at 48 Hours [48 hours]

    2. Time to First Opioid Rescue in the First 48 Hours [48 hours]

      Time to first opioid rescue was estimated from Kaplan-Meier analysis and presented as quartiles (ie, time to rescue for the first 25% / 50% / 75% of subjects within each treatment group).

    3. Overall Benefit of Analgesia Score at 48 Hours [48 hours]

      The overall benefit of analgesic score (OBAS) comprises seven questions to assess pain intensity, adverse effects, and patients' satisfaction with analgesia (eg, "Please rate your current pain at rest on a scale between 0=minimal pain and 4=maximum imaginable pain"). Overall scores ranged between 0- 28. OBAS measures patients' benefit from postoperative pain therapy. A lower composite score indicates greater benefit from the therapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male or female, at least 18 years of age at screening.

    2. Scheduled to undergo primary, unilateral, tricompartmental TKA under spinal anesthesia.

    3. Primary indication for TKA is degenerative osteoarthritis of the knee.

    4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.

    5. 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.

    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. History of previous prior contralateral TKA or open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.

    3. Planned concurrent surgical procedure (e.g., bilateral TKA).

    4. Undergoing unicompartmental TKA or revision TKA.

    5. 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).

    6. Comorbidity impacting current physical function of Investigator opinion that it may impact postsurgical rehabilitation.

    7. Allergy, hypersensitivity, or contraindication to any of the study medications (i.e., bupivacaine, pregabalin, acetaminophen/paracetamol, celecoxib, oxycodone, morphine, hydromorphone, or tranexamic acid).

    8. 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.

    9. 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.

    10. Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.

    11. Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration.

    12. History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion).

    13. 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).

    14. Rheumatoid or inflammatory arthritis or disease.

    15. 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.)

    16. Any neurologic or psychiatric disorder that might impact postsurgical pain or interfere with study assessments.

    17. Malignancy in the last 2 years, per physician discretion.

    18. History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol.

    19. Failure to pass the alcohol breath test or urine drug screen.

    20. Body weight <50 kg (110 pounds) or a body mass index >40 kg/m2.

    21. Previous participation in an EXPAREL study.

    22. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Institute for Joint Restoration Fremont California United States 94538
    2 Loma Linda University Loma Linda California United States 92354
    3 Holy Cross Hospital Fort Lauderdale Florida United States 33334
    4 Cleveland Clinic Florida Weston Florida United States 33331
    5 Pinnacle Orthopaedics & Sports Marietta Georgia United States 30060
    6 Central DuPage Hospital, Northwestern Medicine Winfield Illinois United States 60190
    7 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    8 Orthopaedic Associates Towson Maryland United States 21204
    9 NYU Hospital for Joint Disease New York New York United States 10003
    10 Lenox Hill Hospital/Northwell Health Orthopaedic Institute New York New York United States 10075
    11 UNC Orthopaedics Chapel Hill Chapel Hill North Carolina United States 27599
    12 OrthoCarolina, PA Charlotte North Carolina United States 28207
    13 Wellington Orthopaedics and Sports Medicine Cincinnati Ohio United States 45209
    14 Cleveland Clinic Cleveland Ohio United States 44195
    15 San Antonio Military Medical Center Fort Sam Houston Texas United States 78234
    16 Baylor Medical Center, Plano Orthopedics Sports Medical & Spine Center Frisco Texas United States 75034
    17 Utah University Orthopedic Center Salt Lake City Utah United States 84108

    Sponsors and Collaborators

    • Pacira Pharmaceuticals, Inc

    Investigators

    • Study Director: James B Jones, MD, PharmD, Pacira Pharmaceuticals, Inc

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Pacira Pharmaceuticals, Inc
    ClinicalTrials.gov Identifier:
    NCT02713490
    Other Study ID Numbers:
    • 402-C-331
    First Posted:
    Mar 18, 2016
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited between April 18, 2016 and February 8, 2017 at 16 sites in the United States
    Pre-assignment Detail A total of 167 patients were screened; there were 27 screen failures, including 2 patients who were randomized in error to the EXPAREL 266 mg + bupivacaine hydrochloride (HCl) group.
    Arm/Group Title EXPAREL 266 mg + Bupivacaine HCl Bupivacaine HCl
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Period Title: Overall Study
    STARTED 71 69
    COMPLETED 68 67
    NOT COMPLETED 3 2

    Baseline Characteristics

    Arm/Group Title EXPAREL Bupivacaine Total
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline Total of all reporting groups
    Overall Participants 70 69 139
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.7
    (8.61)
    65.8
    (7.21)
    65.8
    (7.92)
    Sex: Female, Male (Count of Participants)
    Female
    43
    61.4%
    39
    56.5%
    82
    59%
    Male
    27
    38.6%
    30
    43.5%
    57
    41%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    5.7%
    1
    1.4%
    5
    3.6%
    Not Hispanic or Latino
    66
    94.3%
    68
    98.6%
    134
    96.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.4%
    0
    0%
    1
    0.7%
    Asian
    0
    0%
    1
    1.4%
    1
    0.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    7
    10%
    5
    7.2%
    12
    8.6%
    White
    61
    87.1%
    61
    88.4%
    122
    87.8%
    More than one race
    1
    1.4%
    2
    2.9%
    3
    2.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    70
    100%
    69
    100%
    139
    100%
    Body mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    32.395
    (5.805)
    31.311
    (5.189)
    31.857
    (5.515)
    VAS pain score (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    1.91
    (2.120)
    1.89
    (2.241)
    1.90
    (2.174)
    American Association of Anesthesiologists classification (Count of Participants)
    1
    3
    4.3%
    2
    2.9%
    5
    3.6%
    2
    45
    64.3%
    40
    58%
    85
    61.2%
    3
    22
    31.4%
    27
    39.1%
    49
    35.3%
    Location of surgery (Count of Participants)
    Left
    31
    44.3%
    25
    36.2%
    56
    40.3%
    Right
    39
    55.7%
    44
    63.8%
    83
    59.7%

    Outcome Measures

    1. Primary Outcome
    Title Area Under The Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores From 12 to 48 Hours
    Description 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."
    Time Frame From 12-48 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Measure Participants 69 69
    Least Squares Mean (Standard Error) [cm*hr]
    181.523
    (10.786)
    208.407
    (10.814)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EXPAREL, Bupivacaine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0381
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter LSMD
    Estimated Value -26.884
    Confidence Interval (2-Sided) 95%
    -56.608 to 2.841
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Total Postsurgical Opioid Consumption Through 48 Hours
    Description Total postsurgical opioid consumption (converted to oral morphine equivalents) through 48 hours
    Time Frame 0-48 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Measure Participants 70 69
    Least Squares Mean (Standard Error) [mg]
    16.321
    (6.684)
    80.328
    (33.249)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EXPAREL, Bupivacaine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0029
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter LSM treatment ratio
    Estimated Value 0.203
    Confidence Interval (2-Sided) 95%
    0.065 to 0.631
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Opioid-free Subjects at 48 Hours
    Description
    Time Frame 48 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Measure Participants 70 69
    Count of Participants [Participants]
    7
    10%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EXPAREL, Bupivacaine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0088
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Treatment difference
    Estimated Value 0.098
    Confidence Interval (2-Sided) 95%
    0.0284 to 0.1685
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Time to First Opioid Rescue in the First 48 Hours
    Description Time to first opioid rescue was estimated from Kaplan-Meier analysis and presented as quartiles (ie, time to rescue for the first 25% / 50% / 75% of subjects within each treatment group).
    Time Frame 48 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Measure Participants 70 69
    First quartile
    2.617
    1.00
    Median quartile
    4.125
    2.917
    Third quartile
    9.667
    7.200
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EXPAREL, Bupivacaine
    Comments Analysis applies to the overall distribution of time to first opioid rescue, estimated from Kaplan-Meier analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0230
    Comments
    Method Log Rank
    Comments
    5. Secondary Outcome
    Title Overall Benefit of Analgesia Score at 48 Hours
    Description The overall benefit of analgesic score (OBAS) comprises seven questions to assess pain intensity, adverse effects, and patients' satisfaction with analgesia (eg, "Please rate your current pain at rest on a scale between 0=minimal pain and 4=maximum imaginable pain"). Overall scores ranged between 0- 28. OBAS measures patients' benefit from postoperative pain therapy. A lower composite score indicates greater benefit from the therapy.
    Time Frame 48 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    Measure Participants 70 69
    Mean (Standard Deviation) [score on a scale]
    4.1
    (4.08)
    4.6
    (4.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EXPAREL, Bupivacaine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4285
    Comments
    Method Kruskal-Wallis
    Comments

    Adverse Events

    Time Frame From screening to postsurgical day 29
    Adverse Event Reporting Description An AE was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov. Note that 71 subjects were randomized into the EXPAREL arm, but only 70 subjects received EXPAREL.
    Arm/Group Title EXPAREL Bupivacaine
    Arm/Group Description Local infiltration analgesia with EXPAREL (bupivacaine liposome injectable suspension) 266 mg/20 mL admixed with bupivacaine HCl 0.5% 20 mL and expanded with 80 mL normal saline Local infiltration analgesia with bupivacaine HCl 0.5% 20 mL expanded with 100 mL normal saline
    All Cause Mortality
    EXPAREL Bupivacaine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/70 (0%) 0/69 (0%)
    Serious Adverse Events
    EXPAREL Bupivacaine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/70 (1.4%) 1/69 (1.4%)
    Infections and infestations
    Incision site cellulitis 1/70 (1.4%) 0/69 (0%)
    Influenza 0/70 (0%) 1/69 (1.4%)
    Other (Not Including Serious) Adverse Events
    EXPAREL Bupivacaine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 45/70 (64.3%) 39/69 (56.5%)
    Blood and lymphatic system disorders
    Anemia 1/70 (1.4%) 3/69 (4.3%)
    Cardiac disorders
    Bradycardia 2/70 (2.9%) 1/69 (1.4%)
    Gastrointestinal disorders
    Nausea 21/70 (30%) 22/69 (31.9%)
    Vomiting 5/70 (7.1%) 5/69 (7.2%)
    Constipation 3/70 (4.3%) 3/69 (4.3%)
    General disorders
    Peripheral swelling 1/70 (1.4%) 3/69 (4.3%)
    Infections and infestations
    Urinary tract infection 2/70 (2.9%) 0/69 (0%)
    Injury, poisoning and procedural complications
    Anemia postoperative 3/70 (4.3%) 1/69 (1.4%)
    Investigations
    Blood osmolarity decreased 2/70 (2.9%) 0/69 (0%)
    Metabolism and nutrition disorders
    Hypokalemia 4/70 (5.7%) 1/69 (1.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/70 (4.3%) 3/69 (4.3%)
    Muscle spasms 6/70 (8.6%) 0/69 (0%)
    Joint swelling 3/70 (4.3%) 1/69 (1.4%)
    Pain in extremity 1/70 (1.4%) 2/69 (2.9%)
    Nervous system disorders
    Dizziness 3/70 (4.3%) 8/69 (11.6%)
    Psychiatric disorders
    Insomnia 3/70 (4.3%) 2/69 (2.9%)
    Mental status change 0/70 (0%) 2/69 (2.9%)
    Skin and subcutaneous tissue disorders
    Pruritis 3/70 (4.3%) 0/69 (0%)
    Vascular disorders
    Hypotension 3/70 (4.3%) 1/69 (1.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Results conducted at Site shall not be published before 1st multicenter publication by Sponsor but can proceed if there is no such publication ≤18 months after study completion/termination at all sites and all data have been received. Before submitting manuscript/materials to an outside person/entity, site shall give Sponsor 60 days to review and comment. Site shall, upon request, further delay publication/presentation for ≤120 days to allow Sponsor to protect its interests in Inventions.

    Results Point of Contact

    Name/Title Pacira Medical Information
    Organization Pacira Pharmaceuticals, Inc.
    Phone 1-855-793-9727
    Email MedInfo@pacira.com
    Responsible Party:
    Pacira Pharmaceuticals, Inc
    ClinicalTrials.gov Identifier:
    NCT02713490
    Other Study ID Numbers:
    • 402-C-331
    First Posted:
    Mar 18, 2016
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Dec 1, 2020