Clinical trial NCT01683071: Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia Following Total Knee Arthroplasty
Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Postoperative Pain
Keywords: Total knee arthroplasty
Analgesia
Pain management
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2012-09-11
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: This is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study in subjects undergoing primary unilateral total knee arthroplasty (TKA) under general or spinal anesthesia. Note: Bupivacaine cannot be used as the spinal anesthetic.

Part 1 During Part 1 of the study, approximately 100 subjects (25 per treatment arm) will be randomized to receive a single dose injection femoral nerve block with either one of three doses of liposome bupivacaine (67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance. Preservative-free normal saline will be added to the 67 mg and 133 mg doses of study drug to achieve a volume of 20 mL.

Part 2 In Part 2 of the study, approximately 180 subjects (randomized 1:1, resulting in approximately 90 liposome bupivacaine subjects and 90 placebo subjects) will receive a single dose injection femoral nerve block with the selected dose level of liposome bupivacaine (i.e., 67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance.

Eligibility criteria: Inclusion Criteria:

1. Male or female, \>=18 years of age.
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. 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.
5. 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. 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.
2. Planned concurrent surgical procedure (e.g., bilateral TKA).
3. 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.
4. 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).
5. 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®).
6. Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
7. Body weight \< 50 kilograms (110 pounds) or a body mass index ≥ 40 kg/m2.
8. Contraindication to hydromorphone, oxycodone, or bupivacaine.
9. 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.
10. Previous participation in a liposome bupivacaine study.
11. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
12. Failure to pass the urine drug screen.
13. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.
14. 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.
15. Current or historical evidence of any clinically significant disease or condition, especially cardiovascular or neurological conditions that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postsurgical course.
16. Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures.
17. Subjects who are planned to receive Entereg® (alvimopan).
18. Subjects who will receive prophylactic antiemetics or planned postsurgical antiemetics given without regard to the subject's emesis needs.
19. Use of dexmedetomidine HCl (Precedex®) within 3 days of surgery.

Primary outcomes:
measure: Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours
timeFrame: 0-72 hours
Secondary outcomes:
measure: Total Postsurgical Opioid Consumption Through 72 Hours
timeFrame: 0-72 hours
measure: Time to First Opioid Rescue Through 72 Hours
timeFrame: 0-72 hours
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: ACHIEVE CLINICAL RESEARCH LLC 2017 Canyon Road Suite 41
state: Alabama
city: Mobile
country: United States
facility: HORIZON RESEARCH GROUP INC 3610 Springhill Memorial Dr. N
state: Alabama
city: Mobile
country: United States
facility: Veritas Research, LLC
state: Alabama
city: Sheffield
country: United States
facility: SHOALS MEDICAL TRIALS INC. 1300 S Montgomery Ave
state: Alabama
city: Phoenix
country: United States
facility: PHOENIX ORTHOPAEDIC SURGEONS 2525 W. Greenway Road Suite 114
state: Arizona
city: Laguna Hills
country: United States
facility: ALLIANCE RESEARCH CENTERS 24411 Health Center Drive Suite 350
state: California
city: San Bernardino
country: United States
facility: ORTHOPADIC SURGERY Loma Linda University Health Care Dept. Pf Orthopaedic Surgery 250 East Caroline Street Suite A
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Diego
country: United States
facility: Ilfeld, Brian (Thornton) UNIVERSITY OF CALIFORNIA, SAN DIEGO 10610 Hunters Glen Drive
state: California
city: DeLand
country: United States
facility: FLORIDA RESEARCH ASSOCIATES, LLC / FLORIDA ORTHOPAEDIC ASSOCIATES 740 W. Plymouth Ave
state: Florida
city: Miami
country: United States
facility: JACKSON MEMORIAL HOSPITAL UNVERSITY OF MIAMI 1611 Nw. 12th Ave C300
state: Florida
city: Pensacola
country: United States
facility: PENSACOLA RESEARCH CONSULTANTS,INC 5149 N.9th Avenue Suite 241
state: Florida
city: Sunrise
country: United States
facility: SHERIDAN CLINICAL RESEARCH, INC. 1613 N. Harrison Parkway Building C Suite 200
state: Florida
city: Tamarac
country: United States
facility: PHOENIX CLINICAL RESEARCH,LLC 7171 N. University Drive Suite 100
state: Florida
city: Kansas City
country: United States
facility: UNIVERSITY OF KANSAS HOSPITAL & MEDICAL CENTER Dept. Of Anesthesiology 3901 Rainbow Blvd. Ms 1034
state: Kansas
city: Troy
country: United States
facility: BEAUMONT HEALTH SYSTEM 44201 Dequindre Road Suite Pob 120
state: Michigan
city: Camden
country: United States
facility: COOPER UNIVERSITY HOSPITAL 1 Cooper Plaza 202 Dorrance Building
state: New Jersey
city: Newark
country: United States
facility: UNIVERSITY OF MEDICINE AND DENSITRY OF NEW JERSEY/NEW JERSEY MEDICAL SCHOOL 185 South Orange Ave. Department of Anesthesiology - MSB E538
state: New Jersey
city: Mount Kisco
country: United States
facility: NORTHERN WESTCHESTER HOSPTIAL Department Of Clinical Trials 400 East Main St.
state: New York
city: New York
country: United States
facility: ST. LUKE-ROOSEVELT HOSPITAL CENTER Dept. Of Anesthesiology 1111 Amsterdam Ave. Travis Bld. 7
state: New York
city: New York
country: United States
facility: INSALL-SCOTT-KELLY INSTITUTE 210 East 64th Street
state: New York
city: Chapel Hill
country: United States
facility: UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Department Of Anesthesiology 101 Manning Drive N0021, Cb 7010
state: North Carolina
city: Cleveland
country: United States
facility: CLEVELAND CLINIC FAIRVIEW HOSPTIAL 1801 Lorain Avenue
state: Ohio
city: Cleveland
country: United States
facility: CLEVELAND CLINIC 9500 Euclid Ave P-77
state: Ohio
city: Hershey
country: United States
facility: PENN STATE MILTON S. HERSHEY MEDICAL CENTER H187,500 University Drive
state: Pennsylvania
city: Philadelphia
country: United States
facility: THOMAS JEFFERSON UNIVERSITY Dept. Of Anesthesiology 111 S. 11th Street Suite G 8490
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC PRESBYTERIAN SHADYSIDE/ DEPT. OF ANESTHESIOLOGY POSNER PAIN CENTER 532 South Aiken Avenue Suite 407
state: Pennsylvania
city: Galveston
country: United States
facility: UNIVERSITY OF TEXAS MEDICAL BRANCH Dept. Chairman, Orthopedic Surgery & Rehabilitation 2.316 Rebecca Sealy Hospital 301 University Blvd.
state: Texas
city: Houston
country: United States
facility: RESEARCH CONCEPTS,GP LLC 921 Gessner Rd. Anesthesia Dept., Classroom F
state: Texas
city: Nassau Bay
country: United States
facility: CHRISTUS ST. JOHN HOSPITAL 18300 St. John Dr., 2nd Floor, Surgery
state: Texas
Study officials:
affiliation: Pacira Pharmaceuticals, Inc
name: Erol Onel, MD
role: STUDY_DIRECTOR
References: