Double-Blinded Randomized Controlled Study Investigating the Efficacy of Exparel (Liposomal Bupivacaine) for Postoperative Pain Relief in Mandibular Third Molar Extractions

The most prevalent complaint after third molar extractions is pain. There have been many modalities and regimens developed to manage post-operative pain, such as modifications in surgical techniques, locally-applied medicaments, and oral analgesics. Recently, liposomal bupivacaine (Exparel) has been FDA approved for single-dose infiltration in the oral cavity in adults and children (6 years or older) to produce extended postsurgical local anesthesia. We hypothesize that the administration of liposomal bupivacaine (Exparel) at the end of third molar extractions will decrease postoperative pain and decrease narcotic use for pain management.

Study Overview

• Status: Completed
• Conditions: Post Operative Pain
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: 0.5% bupivacaine with 1:100,000 epinephrine

Detailed Description

In this study, we will prospectively collect data from all patients receiving bilateral third molar extractions with Exparel versus 0.5% bupivacaine 1:200,000 epinephrine (standard bupivacaine) injections to determine the efficacy of Exparel in reducing postoperative pain. Outcomes measured will be pain intensity based on a numeric scale, date and time when pain completely subsides for each side, adverse events, use of NSAID or acetaminophen outside of prescribed pain regimen, and use of narcotics. The purpose of this research project is to evaluate the use and efficacy of Exparel in postoperative pain management in third molar extractions.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • Herman Ostrow School of Dentistry of USC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients receiving bilateral mandibular third molar extractions at the Herman Ostrow School of Dentistry by an oral & maxillofacial surgery resident.

Exclusion Criteria:

• Patient unable to complete form for four days postoperatively.
• Patient with severe hepatic disease
• Patient with a history of allergy or contraindication to amide-type LA or opioids
• Patient with recent history of antibiotic use within the past thirty days
• Patients with use of long-acting opioids, NSAIDs, aspirin, acetaminophen within 3 days prior to screening.
• Patients who are pregnant.
• Patients receiving additional mandibular teeth extractions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liposomal bupivacaine; A double-blinded randomization process will be used to preoperatively assign patient's left or right side to receive either Exparel (Liposomal bupivacaine) (39.9 mg/3 mL) or standard bupivacaine (5 mg/mL). At the end of the mandibular third molar extraction surgical procedure and at least twenty minutes following the most recent administration of 2% lidocaine with 1:100,000 epinephrine (routine for this procedure), all patients will receive one side of their mandibular infiltrations with 3mL of 1.3% liposomal bupivacaine (Exparel).	Drug: Liposomal bupivacaine; Dosage: 3 mL Frequency: Administer via buccal infiltration technique immediately following mandibular third molar extraction surgery and at least twenty minutes following most recent lidocaine injection.
Active Comparator: 0.5% bupivacaine with 1:200,000 epinephrine; A double-blinded randomization process will be used to preoperatively assign patient's left or right side to receive either Exparel (Liposomal bupivacaine) (39.9 mg/3 mL) or standard bupivacaine (5 mg/mL). At the end of the procedure and at least twenty minutes following the most recent administration of 2% lidocaine with 1:100,000 epinephrine (routine for this procedure), all patients will receive one side of their mandibular infiltrations with 3mL of diluted 0.5% bupivacaine with 1:200,000 epinephrine.	Drug: 0.5% bupivacaine with 1:100,000 epinephrine; Dosage: 3 mL of diluted 0.5% bupivacaine with 1:200,000 epinephrine (2:1 ratio of saline to standard bupivacaine) Frequency: Administer via buccal infiltration technique immediately following mandibular third molar extraction surgery and at least twenty minutes following most recent lidocaine injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Pain	At home questionnaire with a numerical scale (0 - 10 with 0 being least amount of pain and 10 being most amount of pain), to be completed each morning and evening for four days post-operative. Then the cumulative pain rating using the numeric rating scale area under the curve over 96 hours (0 - 960 with 0 being least amount of pain over 96 hours and 960 being the most amount of pain over 96 hours), scaled at the hour-level, is calculated using the trapezoidal method in the caTools package in R, which is a sum of the averages of the numeric rating scale. A higher value is a worse outcome and lower value is a better outcome.	Mean Area under Curve Numeric rating scale scores 96 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NSAID/Acetaminophen Use	Number of Participants with NSAID/Acetaminophen Use	96 hours post-operatively
Oxycodone Use	Number of Participants with oxycodone Use	96 hours post-operatively

Collaborators and Investigators

• Sponsor: University of Southern California

Publications and helpful links

General Publications

• Lieblich SE, Danesi H. Liposomal Bupivacaine Use in Third Molar Impaction Surgery: INNOVATE Study. Anesth Prog. 2017 Fall;64(3):127-135. doi: 10.2344/anpr-64-02-03.
• Youn S, Scheker K, Sheridan S, Hayashi C, Pickering TA, Costandi J. Does Liposomal Bupivacaine Reduce Postoperative Pain Following Third Molar Extractions? A Double-Blinded Randomized Controlled Trial. J Oral Maxillofac Surg. 2025 May;83(5):592-600. doi: 10.1016/j.joms.2025.01.004. Epub 2025 Jan 17.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): May 1, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Anilides; Amides; Aniline Compounds; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Bupivacaine; Epinephrine
• Other Study ID Numbers: APP2200106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes