Trial Outcomes & Findings for Double-Blinded Randomized Controlled Study Investigating the Efficacy of Exparel (Liposomal Bupivacaine) for Postoperative Pain Relief in Mandibular Third Molar Extractions (NCT NCT05374499)
NCT ID: NCT05374499
Last Updated: 2026-06-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
85 participants
Primary outcome timeframe
Mean Area under Curve Numeric rating scale scores 96 hours post-operatively
Results posted on
2026-06-04
Participant Flow
The initial sample included in the study was composed of 85 subjects. There were 10 subjects who did not return their questionnaire after enrolling in the study, one subject who completed the questionnaire incorrectly and was disqualified, one subject who was excluded due to opioid use during the postoperative period and one subject who was excluded due to postoperative alveolar osteitis.
Unit of analysis: Left or Right Side of Mouth
Participant milestones
| Measure |
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). This is a split-mouth model. 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).
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.
|
Standard 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). This is a split-mouth model. 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).
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.
Standard Bupivacaine (will be added as a unit in the periods section) 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.
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|---|---|---|
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Overall Study
STARTED
|
85 85
|
85 85
|
|
Overall Study
COMPLETED
|
72 72
|
72 72
|
|
Overall Study
NOT COMPLETED
|
13 13
|
13 13
|
Reasons for withdrawal
| Measure |
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). This is a split-mouth model. 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).
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.
|
Standard 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). This is a split-mouth model. 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).
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.
Standard Bupivacaine (will be added as a unit in the periods section) 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.
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|---|---|---|
|
Overall Study
Lost to Follow-up
|
10
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10
|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Did not complete questionnaire correctly
|
1
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
All Participants
n=72 Participants
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).
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.
Standard Bupivacaine 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.
|
|---|---|
|
Age, Continuous
|
25.8 years
STANDARD_DEVIATION 9 • n=72 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=72 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=72 Participants
|
|
Region of Enrollment
United States
|
72 Participants
n=72 Participants
|
PRIMARY outcome
Timeframe: Mean Area under Curve Numeric rating scale scores 96 hours post-operativelyAt 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.
Outcome measures
| Measure |
Liposomal Bupivacaine
n=72 Participants
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).
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.
|
0.5% Bupivacaine With 1:200,000 Epinephrine
n=72 Participants
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.
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.
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|---|---|---|
|
Post-operative Pain
|
548.5 score on a scale*hours
Interval 474.52 to 622.48
|
642 score on a scale*hours
Interval 558.7 to 725.3
|
SECONDARY outcome
Timeframe: 96 hours post-operativelyNumber of Participants with NSAID/Acetaminophen Use
Outcome measures
| Measure |
Liposomal Bupivacaine
n=72 Participants
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).
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.
|
0.5% Bupivacaine With 1:200,000 Epinephrine
n=72 Participants
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.
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.
|
|---|---|---|
|
NSAID/Acetaminophen Use
|
43 Participants
|
43 Participants
|
SECONDARY outcome
Timeframe: 96 hours post-operativelyNumber of Participants with oxycodone Use
Outcome measures
| Measure |
Liposomal Bupivacaine
n=72 Participants
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).
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.
|
0.5% Bupivacaine With 1:200,000 Epinephrine
n=72 Participants
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.
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.
|
|---|---|---|
|
Oxycodone Use
|
1 Participants
|
1 Participants
|
Adverse Events
Liposomal Bupivacaine
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
0.5% Bupivacaine With 1:200,000 Epinephrine
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Liposomal Bupivacaine
n=72 participants at risk
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).
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.
|
0.5% Bupivacaine With 1:200,000 Epinephrine
n=72 participants at risk
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.
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.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.3%
6/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
8.3%
6/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
|
General disorders
Headache
|
16.7%
12/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
16.7%
12/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
|
General disorders
Lightheadedness
|
8.3%
6/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
8.3%
6/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
|
General disorders
Fever
|
2.8%
2/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
2.8%
2/72 • All side effects/toxicities that will be monitored immediately following the injection of Exparel are allergic reactions, paresthesia, dysgeusia, nausea, vomiting, lightheadedness, diaphoresis, palpitations, fever, tinnitus, twitching, blurred vision and headache. Long-term toxicities to be monitored after completion of therapy are paresthesia, dysgeusia, nausea, constipation, fever, vomiting, lightheadedness, diaphoresis, palpitations, and headache up to 96 hours following the procedure.
Unexpected toxicities will be reported via incident reporting form to Office of Clinical Affairs at the Herman Ostrow School of Dentistry, and life-threatening or fatal toxicities (myocardial infarction, cerebrovascular accident) will be reported to the Dental Board of California on the same day and must include the time, date, location, and events that preceded the incident.
|
Additional Information
John Costandi DMD, MD, Oral an Maxillofacial Surgeon
University of Southern California
Phone: 3232434422
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place