Efficacy, Safety, and Pharmacokinetics of Brachial Plexus Block With EXPAREL in Shoulder Surgery

NCT ID: NCT02713230

Last Updated: 2020-12-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

156 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-09

Study Completion Date

2017-07-07

Brief Summary

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This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 155 adult subjects undergoing primary unilateral total shoulder arthroplasty or rotator cuff repair with general anesthesia

Detailed Description

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On Day 0, eligible subjects will be randomized in a 1:1 ratio to receive a single dose of EXPAREL 133 mg in 10 mL expanded in volume with 10 mL of normal saline for a total volume of 20 mL or placebo 20 mL. Study drug (EXPAREL or placebo) will be administered in a blinded manner via an ultrasound guided single-dose brachial plexus block at least 1 hour prior to surgery.

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; 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 is signed through postsurgical Day 29.

Follow-up visits will be scheduled for all subjects on postsurgical Days 5 and 10. A follow-up phone call will be made on postsurgical Day 29.

A population Pharmacokinetic (PK) analysis will be utilized to limit the number of blood draws with a sampling schedule of baseline (prior to the nerve block) through hospital discharge. There will be two collection sequences for this study and a subject can only be randomized to one sequence.

Conditions

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Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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EXPAREL 133 mg

10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively

Group Type ACTIVE_COMPARATOR

bupivacaine liposome injectable suspension

Intervention Type DRUG

10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline

EXPAREL 266 mg

20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively

Group Type ACTIVE_COMPARATOR

bupivacaine liposome injectable suspension

Intervention Type DRUG

20 mL EXPAREL (bupivacaine liposome injectable suspension)

Placebo

20 mL normal saline as single-injection brachial plexus block (interscalene or supraclavicular) ≥1 h preoperatively

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

20 mL normal saline as single-injection

Interventions

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bupivacaine liposome injectable suspension

10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline

Intervention Type DRUG

bupivacaine liposome injectable suspension

20 mL EXPAREL (bupivacaine liposome injectable suspension)

Intervention Type DRUG

Placebo

20 mL normal saline as single-injection

Intervention Type DRUG

Other Intervention Names

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EXPAREL EXPAREL Normal saline

Eligibility Criteria

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Inclusion Criteria

1. Male or female, at least 18 years of age at screening.
2. Scheduled to undergo primary unilateral total shoulder arthroplasty or rotator cuff repair.
3. Subjects scheduled for rotator cuff repair must have a magnetic resonance imaging (MRI) with a reading confirming a tear of at least 1 cm.
4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
5. 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.
6. Able to demonstrate normal motor function (by obtaining a 5 on the Lovett Scale when exhibiting biceps, wrist, and thumb movement) and sensory function (by exhibiting sensitivity to cold, pinprick, and light touch) in the location where sensory function will be measured throughout the study: 2 cm superior to the coracoid process on the skin overlying the acromioclavicular joint.
7. 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.
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 shoulder surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints, chronic neuropathic pain).
4. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.
5. Smoking history of greater than 25 pack-years.
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 medications 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 hydrochloride (HCl) (Precedex®) within 3 days of study drug administration.
11. History of impaired kidney function, emphysema or other 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pacira Pharmaceuticals, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James B Jones, MD, PharmD

Role: STUDY_DIRECTOR

Pacira Pharmaceuticals, Inc

Locations

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Horizon Research Group, Inc

Mobile, Alabama, United States

Site Status

Denver Metro Orthopedics

Englewood, Colorado, United States

Site Status

Jackson Memorial Hospital/University of Miami

Miami, Florida, United States

Site Status

Pensacola Research Associates

Pensacola, Florida, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Fairview Hospital

Cleveland, Ohio, United States

Site Status

Indiana Regional Medical Center

Indiana, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Chan Soon-Shiong Medical Center

Windber, Pennsylvania, United States

Site Status

Hermann Drive Surgical Hospital

Houston, Texas, United States

Site Status

Westside Surgical Hospital

Houston, Texas, United States

Site Status

Plano Surgical Hospital

Plano, Texas, United States

Site Status

Houston Physician's Hospital

Webster, Texas, United States

Site Status

Southampton Orthopedics Sports Medicine

Franklin, Virginia, United States

Site Status

Ziekenhuis Oost-Limburg

Genk, , Belgium

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Regionshospital Silkeborg

Silkeborg, , Denmark

Site Status

Countries

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United States Belgium Denmark

References

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Patel MA, Gadsden JC, Nedeljkovic SS, Bao X, Zeballos JL, Yu V, Ayad SS, Bendtsen TF. Brachial Plexus Block with Liposomal Bupivacaine for Shoulder Surgery Improves Analgesia and Reduces Opioid Consumption: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial. Pain Med. 2020 Feb 1;21(2):387-400. doi: 10.1093/pm/pnz103.

Reference Type DERIVED
PMID: 31150095 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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402-C-327

Identifier Type: -

Identifier Source: org_study_id