Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia Following Total Knee Arthroplasty

NCT01683071 | Completed Phase 2 Results DMC

• 1 other identifier: 402-C-323
• Study Type: interventional
• Target: 297
• Locations: 1 country
• Sites: 30

Brief Summary

The primary objectives of Part 1 are to (1) evaluate three dose levels of liposome bupivacaine versus placebo with respect to the magnitude and duration of the analgesic effect achieved following single dose injection femoral nerve block with liposome bupivacaine, and (2) select a single therapeutic dose of liposome bupivacaine from the three dose levels to be tested in Part 2. Part 2: The primary objective of Part 2 is to compare the magnitude and duration of the analgesic effect of single injection femoral nerve block of a single dose level of liposome bupivacaine (selected from Part 1) with placebo (preservative-free normal saline).

Conditions

Postoperative Pain

Keywords

Total knee arthroplasty; Analgesia; Pain management

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours

  AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)

  0-72 hours

Secondary Outcomes (2)

• Total Postsurgical Opioid Consumption Through 72 Hours

  0-72 hours

• Time to First Opioid Rescue Through 72 Hours

  0-72 hours

Study Arms (6)

(Part 1) EXPAREL 67 mg

EXPERIMENTAL

5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively

Drug: EXPAREL 67 mg

(Part 1) EXPAREL 133 mg

EXPERIMENTAL

10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively

Drug: EXPAREL 133 mg

(Part 1) EXPAREL 266 mg

EXPERIMENTAL

20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively

Drug: EXPAREL 266 mg

(Part 1) Placebo

PLACEBO COMPARATOR

20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively

Drug: Placebo

(Part 2) EXPAREL 266 mg

EXPERIMENTAL

20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively

Drug: EXPAREL 266 mg

(Part 2) Placebo

PLACEBO COMPARATOR

20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively

Drug: Placebo

Interventions

Placebo DRUG

Normal saline 20 mL as single-injection femoral nerve block prior to total knee arthroplasty

Also known as: Preservative-free normal saline.

(Part 1) Placebo; (Part 2) Placebo

EXPAREL 67 mg DRUG

5 mL EXPAREL expanded with 15 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty

Also known as: Bupivacaine liposome injectable suspension 67 mg/5 mL

(Part 1) EXPAREL 67 mg

EXPAREL 133 mg DRUG

10 mL EXPAREL expanded with 10 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty

Also known as: Bupivacaine liposome injectable suspension 133 mg/10 mL

(Part 1) EXPAREL 133 mg

EXPAREL 266 mg DRUG

20 mL EXPAREL as single-injection femoral nerve block prior to total knee arthroplasty

Also known as: Bupivacaine liposome injectable suspension 266 mg/20 mL

(Part 1) EXPAREL 266 mg; (Part 2) EXPAREL 266 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, \>=18 years of age.
• Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
• American Society of Anesthesiologists (ASA) Physical Status 1, 2, or 3.
• Able to demonstrate motor function by performing a 20-meter walk, unassisted with the optional use of a 4-legged walker, and sensory function by exhibiting sensitivity to cold.
• Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

You may not qualify if:

• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Female subjects must be surgically sterile, at least 2 years menopausal, or using an acceptable method of birth control.
• If of childbearing potential, must have a documented negative pregnancy test within 24 hours before surgery.
• Planned concurrent surgical procedure (e.g., bilateral TKA).
• Use of any of the following medications within the times specified before surgery:
• long-acting opioid medication, NSAIDs, aspirin (except for low-dose aspirin used for cardioprotection) or acetaminophen within 3 days, or and any opioid medication within 24 hours.
• Concurrent painful physical condition or concurrent surgery that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the surgical site administered study treatment, and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, prior contralateral TKA, concurrent foot surgery).
• 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 norepinepherine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®).
• Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
• Body weight \< 50 kilograms (110 pounds) or a body mass index ≥ 40 kg/m2.
• Contraindication to hydromorphone, oxycodone, or bupivacaine.
• 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.
• Previous participation in a liposome bupivacaine study.
• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
• Failure to pass the urine drug screen.
• Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (30)

ACHIEVE CLINICAL RESEARCH LLC 2017 Canyon Road Suite 41

Birmingham, Alabama, 35216, United States

Location

HORIZON RESEARCH GROUP INC 3610 Springhill Memorial Dr. N

Mobile, Alabama, 36608, United States

Location

Veritas Research, LLC

Mobile, Alabama, 36660, United States

Location

SHOALS MEDICAL TRIALS INC. 1300 S Montgomery Ave

Sheffield, Alabama, 35660, United States

Location

PHOENIX ORTHOPAEDIC SURGEONS 2525 W. Greenway Road Suite 114

Phoenix, Arizona, 85023, United States

Location

ALLIANCE RESEARCH CENTERS 24411 Health Center Drive Suite 350

Laguna Hills, California, 92653, United States

Location

ORTHOPADIC SURGERY Loma Linda University Health Care Dept. Pf Orthopaedic Surgery 250 East Caroline Street Suite A

San Bernardino, California, 92508, United States

Location

University of California, San Diego

San Diego, California, 92103, United States

Location

Ilfeld, Brian (Thornton) UNIVERSITY OF CALIFORNIA, SAN DIEGO 10610 Hunters Glen Drive

San Diego, California, 92130, United States

Location

FLORIDA RESEARCH ASSOCIATES, LLC / FLORIDA ORTHOPAEDIC ASSOCIATES 740 W. Plymouth Ave

DeLand, Florida, 32720, United States

Location

JACKSON MEMORIAL HOSPITAL UNVERSITY OF MIAMI 1611 Nw. 12th Ave C300

Miami, Florida, 33136, United States

Location

PENSACOLA RESEARCH CONSULTANTS,INC 5149 N.9th Avenue Suite 241

Pensacola, Florida, 32504, United States

Location

SHERIDAN CLINICAL RESEARCH, INC. 1613 N. Harrison Parkway Building C Suite 200

Sunrise, Florida, 33323, United States

Location

PHOENIX CLINICAL RESEARCH,LLC 7171 N. University Drive Suite 100

Tamarac, Florida, 33321, United States

Location

UNIVERSITY OF KANSAS HOSPITAL & MEDICAL CENTER Dept. Of Anesthesiology 3901 Rainbow Blvd. Ms 1034

Kansas City, Kansas, 66160, United States

Location

BEAUMONT HEALTH SYSTEM 44201 Dequindre Road Suite Pob 120

Troy, Michigan, 48085, United States

Location

COOPER UNIVERSITY HOSPITAL 1 Cooper Plaza 202 Dorrance Building

Camden, New Jersey, 08103, United States

Location

UNIVERSITY OF MEDICINE AND DENSITRY OF NEW JERSEY/NEW JERSEY MEDICAL SCHOOL 185 South Orange Ave. Department of Anesthesiology - MSB E538

Newark, New Jersey, 07101, United States

Location

NORTHERN WESTCHESTER HOSPTIAL Department Of Clinical Trials 400 East Main St.

Mount Kisco, New York, 10549, United States

Location

ST. LUKE-ROOSEVELT HOSPITAL CENTER Dept. Of Anesthesiology 1111 Amsterdam Ave. Travis Bld. 7

New York, New York, 10025, United States

Location

INSALL-SCOTT-KELLY INSTITUTE 210 East 64th Street

New York, New York, 10065, United States

Location

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Department Of Anesthesiology 101 Manning Drive N0021, Cb 7010

Chapel Hill, North Carolina, 27599, United States

Location

CLEVELAND CLINIC FAIRVIEW HOSPTIAL 1801 Lorain Avenue

Cleveland, Ohio, 44111, United States

Location

CLEVELAND CLINIC 9500 Euclid Ave P-77

Cleveland, Ohio, 44195, United States

Location

PENN STATE MILTON S. HERSHEY MEDICAL CENTER H187,500 University Drive

Hershey, Pennsylvania, 17033, United States

Location

THOMAS JEFFERSON UNIVERSITY Dept. Of Anesthesiology 111 S. 11th Street Suite G 8490

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC PRESBYTERIAN SHADYSIDE/ DEPT. OF ANESTHESIOLOGY POSNER PAIN CENTER 532 South Aiken Avenue Suite 407

Pittsburgh, Pennsylvania, 15232, United States

Location

UNIVERSITY OF TEXAS MEDICAL BRANCH Dept. Chairman, Orthopedic Surgery & Rehabilitation 2.316 Rebecca Sealy Hospital 301 University Blvd.

Galveston, Texas, 77551, United States

Location

RESEARCH CONCEPTS,GP LLC 921 Gessner Rd. Anesthesia Dept., Classroom F

Houston, Texas, 77024, United States

Location

CHRISTUS ST. JOHN HOSPITAL 18300 St. John Dr., 2nd Floor, Surgery

Nassau Bay, Texas, 77058, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Agnosia

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Results Point of Contact

• Title: Pacira Medical Information
• Organization: Pacira Pharmaceuticals, Inc.

MedInfo@pacira.com

1-855-793-9727

Study Officials

• Erol Onel, MD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 11, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 9, 2020
• Results First Posted: December 9, 2020

Record last verified: 2020-11

Locations

US (30)