Post Operative PainPhase 4NCT05374499
Double-Blinded Randomized Controlled Study Investigating the Efficacy of Exparel (Liposomal Bupivacaine) for Postoperative Pain Relief in Mandibular Third Molar Extractions
A Phase 4 study testing Liposomal bupivacaine and 0.5% bupivacaine with 1:100,000 epinephrine in people with Post Operative Pain, run by University of Southern California at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 14 years and olderHealthy volunteers can take part
- Conditions the study is for
- Post Operative Pain
- What is being tested?
- Liposomal bupivacaine and 0.5% bupivacaine with 1:100,000 epinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 1 May 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients receiving bilateral mandibular third molar extractions at the Herman Ostrow School of Dentistry by an oral \& maxillofacial surgery resident.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Herman Ostrow School of Dentistry of USC
Los Angeles, California, 90089
About this study
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.
Read the 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.
- Conditions
- Post Operative Pain
- Being tested
- Liposomal bupivacaine, 0.5% bupivacaine with 1:100,000 epinephrine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal bupivacaineDrug
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.
0.5% bupivacaine with 1:100,000 epinephrineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Liposomal bupivacaine | Experimental | 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). Receives: Drug: Liposomal bupivacaine |
| 0.5% bupivacaine with 1:200,000 epinephrine | Active comparator | 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. Receives: Drug: 0.5% bupivacaine with 1:100,000 epinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Mean Area under Curve Numeric rating scale scores 96 hours post-operatively
Secondary outcomes (2)
NSAID/Acetaminophen Use
Number of Participants with NSAID/Acetaminophen Use
Measured: 96 hours post-operatively
Oxycodone Use
Number of Participants with oxycodone Use
Measured: 96 hours post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2022
- Study start1 Sep 2022
- Primary completion1 Dec 2023
- Study completion1 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Post Operative PainStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Costandi, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05374499
- Sponsor's protocol ID
- APP2200106
- Status last verified
- Jun 2026
- First submitted
- 10 May 2022
- Last updated
- 4 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD will be shared with other researchers
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.
PubMed 28858553Youn 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.
PubMed 39900116
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blinded Randomized Controlled Study Investigating the Efficacy of Exparel (Liposomal Bupivacaine) for Postoperative Pain Relief in Mandibular Third Molar Extractions
- ClinicalTrials.gov ID
- NCT05374499
- Acronym / sponsor ID
- APP2200106
- Conditions
- Post Operative Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 16 May 2022 (actual)
- Results
- Posted 4 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liposomal bupivacaine | Experimental | Drug: Liposomal bupivacaineA 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). |
| 0.5% bupivacaine with 1:200,000 epinephrine | Active comparator | Drug: 0.5% bupivacaine with 1:100,000 epinephrineA 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. |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patients receiving bilateral mandibular third molar extractions at the Herman Ostrow School of Dentistry by an oral \& maxillofacial surgery resident.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal bupivacaineDosage: 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. | Drug | Liposomal bupivacaine |
| 0.5% bupivacaine with 1:100,000 epinephrineDosage: 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. | Drug | 0.5% bupivacaine with 1:200,000 epinephrine |
Primary outcome
Post-operative Pain
Time frame: Mean Area under Curve Numeric rating scale scores 96 hours post-operatively
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.
2 secondary outcomes
NSAID/Acetaminophen Use
Time frame: 96 hours post-operatively
Oxycodone Use
Time frame: 96 hours post-operatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28858553Lieblich 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.
- Derived from this study: PubMed 39900116Youn 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.
- Individual participant dataSharing planned: No. No IPD will be shared with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liposomal bupivacaine and 0.5% bupivacaine with 1:100,000 epinephrine in people with Post Operative Pain, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-operative Pain (time frame: Mean Area under Curve Numeric rating scale scores 96 hours post-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05374499, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026; AzTrials last refreshed its copy on 6 Nov 2026.