Liposome Bupivacaine for ANKLE Blocks

Ultrasound-guided Specific Blocks of the Distal Tibial and Deep Peroneal Nerves at the Level of the Ankle With a Mixture of Bupivacaine + Liposome Bupivacaine v Bupivacaine Alone v General Anesthesia

Postoperative analgesia for hallux valgus surgery (bunionectomy) is inconsistent and may even result in rebound pain when the (ankle) blocks wear off. It is hypothesized that the mixture of bupivacaine and liposome bupivacaine increases the extent and duration of postoperative analgesia and decreases opioid consumption as compared to bupivacaine alone or to general anesthesia.

Study Overview

• Status: Completed
• Conditions: Hallux Valgus (Bunions)
• Intervention / Treatment: Drug: Liposome bupivacaine

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, B-3600
    • Ziekenhuis Oost-Limburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, at least 18 years and max 65 years of age at screening
• Scheduled to undergo primary Scarf osteotomy for elective hallux valgus
• American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
• Female subject must be surgically sterile or have a monogamous partner who is surgically sterile; or be at least 2 years postmenopausal; or practicing abstinence; 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 demonstrate sensory function by exhibiting sensitivity to cold, pinprick, and light touch
• Able to understand the English or Dutch language, purpose and risks of the study, provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations
• Able to adhere to the study visit schedule, and complete all study assessments.

Exclusion Criteria:

• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration
• Planned concurrent surgical procedure (e.g., bilateral hallux valgus repair)
• 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 hallux valgus and which may confound the postsurgical assessments (e.g., significant pain from other joints including chronic neuropathic pain, concurrent or prior contralateral knee or foot surgery)
• Previous hallux valgus on the foot being considered for surgery
• History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics
• Contraindication to bupivacaine, oxycodone, morphine, or hydromorphone
• Chronic daily use of long-acting opioid medication or NSAIDs (except for low-dose aspirin used for cardioprotection) 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 study enrollment
• Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration
• History of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in the extremities
• 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
• Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments
• Any chronic neuromuscular deficit affecting the peripheral nerves or muscles of the surgical extremity
• Any chronic condition or disease that would compromise neurological or vascular assessments
• Suspected or known history of drug or alcohol abuse within the previous year
• Body weight <40 kg (88 pounds) or a body mass index >44 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single mixture LB & bupivacaine; A single mixture of liposome bupivacaine 1.3% (5 mL) + bupivacaine 0.5% (2.5 mL) injected into the distal tibial and deep peroneal nerves	Drug: Liposome bupivacaine
Active Comparator: Bupivacaine alone; Bupivacaine 0.5% (7.5 mL) injected into the distal tibial and deep peroneal nerves	Drug: Liposome bupivacaine
Sham Comparator: General anesthesia	Drug: Liposome bupivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in current pain over the first postoperative week	Pain rating (NRS) at rest and with movement	From baseline (before nerve block) through first postoperative week
Change in worst pain over the first postoperative week	Modified BRIEF Pain Inventory (Q1)	From discharge from PACU through first postoperative week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Self-reported consumption of Tramadol tablets	From hospital discharge through first postoperative week
Change in ability to use foot	Stand with equal weight on both feet, wiggle toes, walk 10 steps	From discharge from PACU through first postoperative week
Change in sleep quality	Duration (h), quality rating (0 - 10)	From discharge from PACU through first postoperative week
Change in satisfaction with pain control	With pain control (0 - 10)	From discharge from PACU through first postoperative week
Change in sensory response in skin dermatomes	Cold, pinprick, light touch in the distal tibial and deep peroneal nerve dermatomes	From premedication through first postoperative week
Change in motor response in foot	Plantar flexion, dorsiflexion	From premedication through first postoperative week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of participants with side effects to regional anesthesia peripheral nerve blockade	Nausea, vomiting, fever, constipation, severe itching of the skin, dizziness, sleepless nights, excessive sweating, urinary retention, headache, heart palpitations	From beginning of nerve block through first postoperative week
Participants with adverse events	Any untoward medical occurrence (unfavorable and/or unintended change in a body structure or body function) associated with the use of a drug in humans, whether or not considered drug related	From date of signing ICF through first postoperative week

Collaborators and Investigators

• Sponsor: Catherine Vandepitte, M.D.
• Collaborators: Pacira Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): June 26, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 10, 2017

Study Record Updates

• Last Update Posted (Actual): September 11, 2020
• Last Update Submitted That Met QC Criteria: September 9, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Foot Deformities; Hallux Valgus; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 1602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No