Bupivacaine and Liposomal Bupivacaine for Postoperative Pain

Overseen By John Costandi

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Southern California

Must not be taking: Long-acting opioids, NSAIDs

Disqualifiers: Severe hepatic disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if liposomal bupivacaine, a longer-lasting pain relief medicine, can reduce pain and the need for narcotics after wisdom tooth removal. Participants will receive either this new treatment or standard bupivacaine, and researchers will compare the results. Individuals undergoing removal of both lower wisdom teeth at the Herman Ostrow School of Dentistry, without a history of certain allergies or recent medication use, might be suitable for this trial. As a Phase 4 trial, this research seeks to understand how this FDA-approved treatment benefits more patients, contributing to broader pain management strategies.

Will I have to stop taking my current medications?

Yes, you will need to stop taking long-acting opioids, NSAIDs (non-steroidal anti-inflammatory drugs), aspirin, and acetaminophen at least 3 days before the trial.

What is the safety track record for these treatments?

Research shows that liposomal bupivacaine, also known as Exparel, reduces pain at the surgery site in dental procedures and lessens the need for opioids. Studies have found that this treatment is generally well-tolerated, aiming to relieve pain with minimal side effects. The FDA has approved its use in the mouth for adults and children over six, indicating its safety.

When compared to regular bupivacaine, another common pain reliever, liposomal bupivacaine has shown mixed results. Some studies did not find it more effective at controlling pain or reducing opioid use. However, it can sometimes shorten hospital stays and reduce the need for opioid refills.

In summary, both liposomal bupivacaine and regular bupivacaine are generally safe and manage pain after surgery with few side effects. However, their effectiveness in controlling pain can vary. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about liposomal bupivacaine for postoperative pain because it offers a prolonged release of the anesthetic, potentially providing longer-lasting pain relief compared to standard bupivacaine. While traditional bupivacaine is effective, it typically has a shorter duration of action. Liposomal bupivacaine, marketed as Exparel, uses a novel delivery system that allows the drug to be released slowly over time, which could reduce the need for additional pain medications post-surgery. This extended action is especially promising for patients undergoing procedures like wisdom tooth extractions, where managing pain effectively and efficiently is crucial.

What evidence suggests that this trial's treatments could be effective for postoperative pain?

Research has shown that liposomal bupivacaine (Exparel), one of the treatments studied in this trial, can manage pain more effectively after certain surgeries, such as hernia repairs and bunion removals, compared to regular bupivacaine. However, some studies found it does not always provide better pain relief than regular bupivacaine or other pain treatments. In many trials, it did not significantly reduce pain more than standard treatments. Despite these mixed results, liposomal bupivacaine has significantly reduced pain and lowered the need for opioids for up to 72 hours after surgery in some cases. This suggests it might reduce the need for pain medication after surgery, but its effectiveness can vary depending on the type of surgery and the patient. In this trial, participants will receive either liposomal bupivacaine or standard bupivacaine to assess their effectiveness in managing postoperative pain. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

Inclusion Criteria

You are having surgery to remove both of your back wisdom teeth at a specific dental school.

Exclusion Criteria

Patients who are pregnant.

You have a serious liver disease.

Patient unable to complete form for four days postoperatively.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo bilateral third molar extractions with either Exparel or standard bupivacaine

1 day

1 visit (in-person)

Follow-up

Participants complete at-home questionnaires to monitor post-operative pain and medication use

1 week

No in-person visits, daily at-home questionnaires

What Are the Treatments Tested in This Trial?

Interventions

• 0.5% bupivacaine with 1:100,000 epinephrine
• Liposomal bupivacaine

How Is the Trial Designed?

Group I: Liposomal bupivacaine Experimental Treatment 1 Intervention

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).

Group II: 0.5% bupivacaine with 1:200,000 epinephrine Active Control 1 Intervention

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.

Liposomal bupivacaine is already approved in United States, European Union for the following indications:

Approved in United States as Exparel for:

• Postsurgical pain in adults

Approved in European Union as Exparel liposomal for:

• Local pain relief around small to medium-sized surgical wounds
• Regional pain relief in the surgery of the knee and around the shoulders

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

In a study involving 59 patients undergoing total knee arthroplasty, liposomal bupivacaine did not show a significant clinical advantage over standard bupivacaine in terms of postoperative recovery, as measured by the number of physical therapy sessions needed for discharge.

The use of liposomal bupivacaine was associated with higher medication charges, raising concerns about its cost-effectiveness compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. Hyland, SJ., Deliberato, DG., Fada, RA., et al.[2019]

In a study of 50 patients undergoing vaginal reconstructive surgery, liposomal bupivacaine (LB) did not show any significant advantage over plain bupivacaine in terms of postoperative pain control, narcotic use, or length of hospital stay.

Despite LB's higher cost, the results indicate that it is not more effective than plain bupivacaine for managing pain after surgery, suggesting a need for further research to find the best pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. Jensen, S., Amasyali, AS., Keheila, M., et al.[2023]

A review of 76 randomized controlled trials found that only 11% showed a significant benefit of liposomal bupivacaine over standard bupivacaine or ropivacaine for postoperative pain control.

The majority of trials indicated that unencapsulated bupivacaine provided better pain relief than liposomal bupivacaine, suggesting that routine use of liposomal bupivacaine may not be justified based on current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Ilfeld, BM., Eisenach, JC., Gabriel, RA.[2021]

Liposomal bupivacaine (LB) is safe for use in pediatric patients and significantly improves pain control after pharyngoplasty, as evidenced by lower pain scores compared to those receiving standard lidocaine.

Patients treated with LB had earlier oral intake, required fewer opioids, and were discharged from the hospital nearly 2 days earlier than those in the control group, highlighting its efficacy in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. Day, KM., Nair, NM., Griner, D., et al.[2018]

In a pilot study involving 25 pigs, subarachnoid administration of liposomal bupivacaine resulted in a longer duration of pain relief compared to standard bupivacaine hydrochloride, with effects lasting up to 32 hours for higher doses.

No signs of neurotoxicity were observed in any treatment group, suggesting that liposomal bupivacaine may be a safe option for extended analgesia in the neuraxial space, warranting further studies for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. Zel, J., Hadzic, A., Cvetko, E., et al.[2019]

In a study involving 98 mice, liposomal bupivacaine (Exparel®) provided a longer duration of pain relief compared to standard bupivacaine, with motor block lasting up to 180 minutes and thermoalgesic block lasting up to 420 minutes.

The addition of dexamethasone, either perineurally or systemically, significantly reduced neural inflammation caused by bupivacaine, and perineural dexamethasone also helped reduce inflammation from Exparel®, suggesting a protective effect against nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. Ferré, F., Krin, A., Sanchez, M., et al.[2020]

In a retrospective analysis of 575 subjects across 6 clinical trials, liposome bupivacaine showed a similar safety profile to both bupivacaine HCl and normal saline, with 76% of liposome bupivacaine recipients experiencing adverse events (AEs).

The most common AEs for liposome bupivacaine included nausea and hypesthesia, and serious AEs occurred in 8% of subjects, indicating that the side effects are likely related to the surgical procedure rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Ilfeld, BM., Viscusi, ER., Hadzic, A., et al.[2022]

In a study of 34 patients undergoing breast augmentation, liposomal bupivacaine provided statistically significant lower pain scores compared to standard bupivacaine at multiple time points post-surgery, indicating it may offer better pain control.

Despite the statistical significance, the differences in pain relief were small, and 70% of patients felt the additional cost of liposomal bupivacaine was not justified by the benefits, suggesting limited clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Nadeau, MH., Saraswat, A., Vasko, A., et al.[2022]

Bupivacaine liposomal injection has been approved by the FDA as a local anesthetic for managing postsurgical pain in adults, showing significant efficacy in reducing postoperative pain and opioid use compared to placebo.

This review compares the efficacy of bupivacaine liposomal to conventional bupivacaine with or without epinephrine, utilizing both published and unpublished data submitted to the FDA by the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine liposomal versus bupivacaine: comparative review. Noviasky, J., Pierce, DP., Whalen, K., et al.[2021]

Liposomal bupivacaine (Exparel) has been shown to be a safe and effective option for managing postoperative pain in plastic surgery, based on a review of eight studies involving 405 patients.

Compared to traditional pain management methods, liposomal bupivacaine was found to be equivalent or more effective, suggesting it could serve as a less invasive alternative to more complex pain management systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. Vyas, KS., Rajendran, S., Morrison, SD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3772762/

Liposomal extended-release bupivacaine for postsurgical ... EXPAREL® has been found to be a more effective pain management treatment than standard bupivacaine in inguinal hernia repair, bunionectomy, hemorrhoidectomy, ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022480421001244

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ... Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs.

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2790975

Efficacy of Liposomal Bupivacaine and ... This study found that liposomal bupivacaine did not improve postoperative recovery or pain compared with bupivacaine hydrochloride alone among patients ...

4. journalofsurgicalresearch.com journalofsurgicalresearch.com/article/S0022-4804(21)00124-4/abstract

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ... Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs. Of the studies ...

5. aetna.com aetna.com/cpb/medical/data/900_999/0941.html

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ... The authors concluded that bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11614469/

Examining Liposomal Bupivacaine's Use in Dentistry - PMC The purported benefits of liposomal bupivacaine are decreased surgical site pain, increased patient satisfaction, and decreased opioid use, among others.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02969187

Bupivacaine Liposomal Injection (Exparel) for Postsurgical ... The aim of this study is to study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using Exparel versus Bupivacaine as ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777506

Standard vs Liposomal Bupivacaine for Postoperative Pain ... Liposomal bupivacaine did not provide improved pain control and did not reduce adjunctive opioid use compared with conventional bupivacaine formulation over 3 ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S027823912400065X

Liposomal Bupivacaine Suspension Can Reduce the ... The use of LB/regular bupivacaine for mandibular fracture(s) results in decrease in LOS and number of opioid refills compared to regular bupivacaine alone.