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PainPhase 4NCT02713490

Local Infiltration Analgesia With and Without EXPAREL Following Total Knee Arthroplasty

A Phase 4 study testing EXPAREL and Bupivacaine in people with Pain, run by Pacira Pharmaceuticals, Inc at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Pain
What is being tested?
EXPAREL and Bupivacaine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
17 sitesUnited States
Study dates
18 Apr 2016to 8 Feb 2017
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 22Show fewer
  • 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.)
  • Any neurologic or psychiatric disorder that might impact postsurgical pain or interfere with study assessments.
  • Malignancy in the last 2 years, per physician discretion.
  • History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol.
  • Failure to pass the alcohol breath test or urine drug screen.
  • Body weight <50 kg (110 pounds) or a body mass index >40 kg/m2.
  • Previous participation in an EXPAREL study.
  • 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.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites
  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • UNC Orthopaedics Chapel Hill

    Chapel Hill, North Carolina, 27599

  • OrthoCarolina, PA

    Charlotte, North Carolina, 28207

  • Wellington Orthopaedics and Sports Medicine

    Cincinnati, Ohio, 45209

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33334

  • San Antonio Military Medical Center

    Fort Sam Houston, Texas, 78234

  • Institute for Joint Restoration

    Fremont, California, 94538

  • Baylor Medical Center, Plano Orthopedics Sports Medical & Spine Center

    Frisco, Texas, 75034

  • Loma Linda University

    Loma Linda, California, 92354

  • Pinnacle Orthopaedics & Sports

    Marietta, Georgia, 30060

  • NYU Hospital for Joint Disease

    New York, New York, 10003

  • Lenox Hill Hospital/Northwell Health Orthopaedic Institute

    New York, New York, 10075

  • Utah University Orthopedic Center

    Salt Lake City, Utah, 84108

  • Orthopaedic Associates

    Towson, Maryland, 21204

  • Cleveland Clinic Florida

    Weston, Florida, 33331

  • Central DuPage Hospital, Northwestern Medicine

    Winfield, Illinois, 60190

Other trials in United States

About this study

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

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).

Read the 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.

Conditions
Pain
Being tested
EXPAREL, Bupivacaine
Medical subject headings
Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EXPARELDrug

    Also called bupivacaine liposome injectable suspension

    EXPAREL and bupivacaine HCl

  • BupivacaineDrug

    Also called bupivacaine HCl

    Single dose of bupivacaine HCl 0.5%

Study groups in NCT02713490
Study groupRoleWhat they receive
EXPARELActive comparatorSingle 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).
Receives: Drug: EXPAREL
BupivacaineActive comparatorBupivacaine HCl 0.5% in 20 mL expanded in volume with 100 mL normal saline (total volume of 120 mL).
Receives: Drug: Bupivacaine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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."

    Measured: From 12-48 hours

  2. Total Postsurgical Opioid Consumption Through 48 Hours

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

    Measured: 0-48 hours

Secondary outcomes (3)
  1. Percentage of Opioid-free Subjects at 48 Hours

    Measured: 48 hours

  2. Time to First Opioid Rescue in the First 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).

    Measured: 48 hours

  3. Overall Benefit of Analgesia Score at 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.

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2016 (estimated)
  2. Study start18 Apr 2016
  3. Primary completion8 Feb 2017
  4. Study completion8 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02713490
Sponsor's protocol ID
402-C-331
Status last verified
Dec 2020
First submitted
15 Mar 2016
Last updated
11 Dec 2020
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 30799269
  • 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.

    PubMed 28802777

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing EXPAREL and Bupivacaine in people with Pain, run by Pacira Pharmaceuticals, Inc at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under The Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores From 12 to 48 Hours (time frame: From 12-48 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02713490, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2020.

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