Efficacy of EXPAREL vs. Bupivacaine

NCT ID: NCT07212114

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2029-08-31

Brief Summary

The goal of this clinical study is to learn about pain management strategies in subjects undergoing total ankle replacement. arthroplasty surgery The primary objective is to compare the magnitude of the analgesic effect following a single dose injection of EXPAREL vs. 0.25% bupivacaine (HCl).

Secondary objectives are to:

Compare the total opioid consumption (in oral morphine equivalents) from 0 to 96 hours following a single dose injection of EXPAREL vs. 0.25% bupivacaine HCl

• Compare the time to first opioid consumption following a single dose injection of EXPAREL vs. 0.25% bupivacaine HCl
• Assess the safety of EXPAREL vs. 0.25% bupivacaine HCl
• Evaluate subject satisfaction with pain management following a single-dose injection of EXPAREL vs. 0.25% bupivacaine hydrochloride (HCl)
• Compare clinical performance from Preoperative status to 3- and 12- months postoperatively

Detailed Description

EXPAREL® is a long-acting local anesthetic specifically developed to provide extended postsurgical pain relief from a single-dose administration, thereby reducing or eliminating the need for indwelling catheters and minimizing reliance on supplemental opioid medications. It is currently indicated for single-dose infiltration to produce local analgesia in patients aged 6 years and older, as well as for regional analgesia via interscalene brachial plexus, sciatic (in the popliteal fossa), and adductor canal nerve blocks in adults. Pain following surgery is common, often peaking in the initial postoperative days, and if inadequately managed, it can delay healing, impair mobilization, prolong hospital stays, and increase the risk of complications and healthcare costs. Despite the prevalence of multimodal analgesic strategies-including the use of local anesthetics and systemic opioids-opioids remain a mainstay for moderate to severe postsurgical pain. However, their use is often limited by adverse effects such as respiratory depression, nausea, vomiting, pruritus, constipation, somnolence, and urinary retention. These complications not only reduce patient satisfaction and recovery but also increase medical intervention and resource use, making opioid-sparing alternatives clinically and economically attractive.

EXPAREL addresses this need by leveraging a proprietary multivesicular liposome (pMVL) drug delivery system that encapsulates bupivacaine at a concentration of 13.3 mg/mL within microscopic spherical vesicles. These vesicles-composed of naturally occurring or bioanalogous lipids-release bupivacaine gradually over time through lipid membrane reorganization and diffusion, thereby extending its duration of action well beyond the 6-8 hours typical of conventional bupivacaine formulations. The liposomal technology used in EXPAREL is based on the same pMVL platform found in the FDA-approved product DepoCyt®, though EXPAREL's lipid formulation has been modified for local anesthetic use. Since its initial FDA approval in 2011 for surgical site infiltration and the subsequent expansion of its indications in 2018 to include various nerve blocks, EXPAREL has been administered to approximately 14 million patients in the U.S., highlighting its growing adoption in clinical practice.

The rationale for the current study stems from the need to optimize postsurgical pain control in patients undergoing total ankle arthroplasty, a procedure associated with significant postoperative pain. This randomized, double-blind, active-controlled, single-center trial will evaluate the efficacy of EXPAREL when used in combination with bupivacaine HCl as part of a combined sciatic (popliteal fossa) and saphenous (adductor canal) nerve block regimen. Specifically, the intervention group will receive 20 mL EXPAREL (266 mg) admixed with 20 mL of 0.25% bupivacaine HCl (50 mg), while the control group will receive 40 mL of 0.25% bupivacaine HCl (100 mg), with each agent administered in equal volumes to the respective nerve sites. The objective is to determine whether the EXPAREL-based regimen provides more effective and longer-lasting analgesia compared to bupivacaine HCl alone, thereby enhancing recovery, reducing opioid consumption, and improving overall patient outcomes in a high-pain surgical population.

Conditions

Total Ankle Arthroplasty; Postsurgical Analgesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Admix

EXPAREL admixed with 0.25% bupivacaine HCl Total volume (50 mL) will be split such that 30 mL will be administered as the sciatic nerve block (in the popliteal fossa) and 20 mL will be administered as the saphenous nerve block (in the adductor canal)

Group Type: EXPERIMENTAL

EXPAREL

Intervention Type: DRUG

EXPAREL (bupivacaine liposome injectable suspension) is formulated as a sterile, non-pyrogenic, white to off-white, preservative-free homogenous suspension of bupivacaine encapsulated into multivesicular liposomes (pMVL drug delivery system). For this study, EXPAREL will be provided in 20 mL (266 mg) EXPAREL single-use, clear glass vials.

0.25% bupivacaine (HCl): 30 ml

Intervention Type: DRUG

EXPAREL admixed with 30 mL (75 mg) 0.25% bupivacaine HCl

Reference

Bupivacaine HCl arm Total volume (50 mL) will be split such that 30 mL will be administered as the sciatic nerve block (in the popliteal fossa) and 20 mL will be administered as the saphenous nerve block (in the adductor canal)

Group Type: EXPERIMENTAL

0.25% bupivacaine (HCl): 50 ml

Intervention Type: DRUG

The reference product is 50 mL (125 mg) 0.25% bupivacaine HCl administered via a combined sciatic (in the popliteal fossa) and saphenous nerve block (in the adductor canal)

Interventions

EXPAREL

EXPAREL (bupivacaine liposome injectable suspension) is formulated as a sterile, non-pyrogenic, white to off-white, preservative-free homogenous suspension of bupivacaine encapsulated into multivesicular liposomes (pMVL drug delivery system). For this study, EXPAREL will be provided in 20 mL (266 mg) EXPAREL single-use, clear glass vials.

Intervention Type: DRUG

0.25% bupivacaine (HCl): 50 ml

The reference product is 50 mL (125 mg) 0.25% bupivacaine HCl administered via a combined sciatic (in the popliteal fossa) and saphenous nerve block (in the adductor canal)

Intervention Type: DRUG

0.25% bupivacaine (HCl): 30 ml

EXPAREL admixed with 30 mL (75 mg) 0.25% bupivacaine HCl

Intervention Type: DRUG

Other Intervention Names

bupivacaine liposome injectable suspension

Eligibility Criteria

Inclusion Criteria

• Indicated to undergo unilateral total ankle arthroplasty
• American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
• Able to provide informed consent, adhere to the study schedule, and complete all study assessments
• Body Mass Index (BMI) ≥18 and ≤40 kg/m2

Exclusion Criteria

• Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
• Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post-dosing period for pain, and which, in the Investigator's opinion, may confound the post-dosing assessments
• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
• Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance
• Currently pregnant, nursing, or planning to become pregnant during the study
• History of contralateral ankle arthroplasty within 1 year
• Subjects that require ankle arthroplasty due to failed prior ankle arthrodesis
• Subjects with avascular necrosis of the talus
• Subjects undergoing revision total ankle arthroplasty
• Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction or other conditions that would constitute a contraindication to participation in the study
• Chronic opioid use within 30 days before randomization (average ≥30 oral morphine equivalents/day
• Prisoners
• Cognitive impairment or impaired decision-making capacity
• Inability to communicate in English

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pacira Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Sameh Labib

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sameh Labib, MD, FAOA

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Orthopaedic Hospital Musculoskeletal Institute (MSK)

Atlanta, Georgia, United States

Countries

United States

Central Contacts

Sameh Labib, MD, FAOA

Role: CONTACT

slabib@emory.edu

404-778-4398

Facility Contacts

Sameh Labid, MD, FAOA

Role: primary

slabib@emory.edu

404-778-4398

Other Identifiers

STUDY00008684

Identifier Type: -

Identifier Source: org_study_id