Exparel vs Bupivacaine for Postoperative Pain

Overseen By Sandra L Beauclair,, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Case Western Reserve University

Must not be taking: Opioids, NSAIDs, Aspirin, Acetaminophen

Disqualifiers: Pregnancy, Allergy to anesthetics, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate post-operative period

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two pain treatments for individuals undergoing wisdom teeth removal. It compares Exparel (bupivacaine liposome injectable suspension), a new long-lasting pain relief option, with standard bupivacaine to determine which more effectively reduces post-surgery pain. The trial targets adults scheduled to have all four wisdom teeth extracted and who have specific conditions with their lower teeth. The goal is to identify which treatment better manages pain and potentially reduces the need for pain pills after surgery. Participants should not have allergies to certain pain medications or be taking specific drugs before surgery. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader patient population.

Will I have to stop taking my current medications?

The trial requires that you stop using long-acting opioids, nonsteroidal anti-inflammatory drugs, aspirin, or acetaminophen at least 3 days before screening, and opioids within 24 hours of screening.

What is the safety track record for Exparel and standard bupivacaine?

Research has shown that Exparel, a type of pain relief medication, is generally safe for people. Studies have found that common side effects include fever, dizziness, and swelling, occurring in about 2% to 10% of patients. One study confirmed that Exparel is safe for easing pain after surgery in both children and adults. Additionally, a real-world review of reports from the FDA, which monitors drug side effects, found no unusual safety issues compared to regular bupivacaine.

Overall, the evidence suggests that patients tolerate Exparel well, with manageable side effects. This makes it a promising choice for those considering it for pain relief after surgery. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for postoperative pain, which typically involves standard bupivacaine, Exparel is unique because it uses a liposomal formulation. This means that the active ingredient, bupivacaine, is encapsulated in tiny lipid-based particles, allowing for a slower and more controlled release. As a result, Exparel can potentially provide longer-lasting pain relief with a single dose, reducing the need for additional pain medications and their associated side effects. Researchers are excited about Exparel because it could improve patient comfort and recovery times by offering extended pain control without the need for frequent dosing.

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

This trial will compare Exparel, a liposomal bupivacaine, with standard bupivacaine for managing postoperative pain. Research has shown mixed results for Exparel in managing pain after surgery. Some studies found it does not relieve pain better than regular bupivacaine or similar treatments. Specifically, over 74% of studies indicated that Exparel was not significantly more effective than other pain relief options. However, some reports suggest it can significantly control pain after surgery and reduce the need for opioids, which are strong painkillers. These findings are important to consider when evaluating its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Faisal Quereshy, MD

Principal Investigator

Case Western Reserve University

Are You a Good Fit for This Trial?

Adults (18+) scheduled for bilateral third molar extraction with at least partial bony impaction of both mandibular third molars can join. They must be in good health as defined by the American Society of Anesthesiologists (class 1, 2, or 3). Pregnant women cannot participate.

Inclusion Criteria

I am an adult scheduled for wisdom teeth removal under anesthesia and my wisdom teeth are partially or fully impacted.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive mandibular and maxillary infiltrations with either 3mL of 1.3% liposomal bupivacaine (Exparel) or standard bupivacaine following third molar extraction

Immediate post-operative period

1 visit (in-person)

Post-operative Monitoring

Participants complete electronic home questionnaires to evaluate anaesthetic parameters, postoperative analgesia, and oral analgesic consumption for 96 hours

4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exparel

Trial Overview

The study is testing if Exparel (liposomal bupivacaine) provides better post-operative pain control than standard bupivacaine. It's a head-to-head comparison where patients are randomly assigned to receive one of the two drugs.

How Is the Trial Designed?

Group I: liposomal bupivacaine Experimental Treatment 1 Intervention

patient receive mandibular and maxillary infiltrations with 3mL of 1.3% liposomal bupivacaine (Exparel)

Group II: standard bupivicaine Active Control 1 Intervention

patient receive mandibular and maxillary infiltrations with 3mL of standard 3mL standard bupivacaine.

Exparel is already approved in United States for the following indications:

Approved in United States as Exparel for:

• Postsurgical local analgesia via infiltration in patients aged 6 years and older
• Postsurgical regional analgesia via an interscalene brachial plexus block in adults
• Postsurgical regional analgesia via a sciatic nerve block in the popliteal fossa in adults
• Postsurgical regional analgesia via an adductor canal block in adults

Who Is Running the Clinical Trial?

Case Western Reserve University

Lead Sponsor

Trials

314

Recruited

236,000+

Published Research Related to This Trial

EXPAREL® (bupivacaine liposome injectable suspension) is an FDA-approved extended-release anesthetic that significantly reduces postoperative pain and opioid consumption in patients undergoing total knee and hip replacement surgeries, as shown in multiple phase 2 and phase 3 studies.

Using EXPAREL® as part of a multimodal pain management approach leads to better outcomes, including lower pain scores, reduced need for rescue opioids, and improved patient satisfaction during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in incorporation of local analgesics in postsurgical pain pathways. Lombardi, AV.[2014]

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 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 study of 352 patients undergoing shoulder surgery with an Exparel interscalene block, 16.5% experienced postoperative complications, with 6.0% leading to emergency department visits, highlighting the need for careful patient selection.

The American Society of Anesthesiologists (ASA) score was identified as a significant risk factor for both minor and major complications, suggesting that patients with higher ASA scores may be at greater risk when receiving this type of anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for complications and return to the emergency department after interscalene block using liposomal bupivacaine for shoulder surgery. Malige, A., Yeazell, S., Ng-Pellegrino, A., et al.[2021]

EXPAREL® (bupivacaine liposome injectable suspension) is an effective extended-release local anesthetic that can significantly improve postoperative pain management in orthopedic trauma surgery, as demonstrated in two case studies.

Both patients treated with EXPAREL® experienced good control of postsurgical pain, highlighting its safety and efficacy as part of a multimodal analgesia approach in reducing the risk of chronic pain after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. Hutchinson, HL.[2022]

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]

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]

Citations

1.

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.

2.

investor.pacira.com

investor.pacira.com/news-releases/news-release-details/pacira-pharmaceuticals-inc-announces-results-expareltm-pivotal

Release details

The results of this trial demonstrate that EXPAREL provides significant postsurgical pain control with a decreased reliance on opioids and improved patient ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28478185/

Effectiveness of Bupivacaine Liposome Injectable ...

Conclusion: There is no benefit in the use of liposomal bupivacaine compared with ropivacaine for postoperative pain control in TKA.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06547255?term=liposome&viewType=Table&rank=6

Exparel Versus Bupivacaine in Post-operative Pain Control

Study Plan ; Active Comparator : standard bupivicaine. patient receive mandibular and maxillary infiltrations with 3mL of standard 3mL standard bupivacaine.

5.

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 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11975001/

Real-World Pharmacovigilance Analysis of Adverse Events ...

This study analyzed adverse events (AEs) associated with liposomal bupivacaine and bupivacaine using the FDA Adverse Event Reporting System (FAERS) database

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf

EXPAREL (bupivacaine liposome injectable suspension)

The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration were pyrexia, dizziness, edema ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468428725000784

Liposomal bupivacaine infiltration for postprocedural ...

These findings suggest that LB is safe to use for postprocedural analgesia in pediatric and adult patients undergoing painful interventions for vascular ...

9.

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 ...

10.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30521078/

Incidence of adverse events attributable to bupivacaine ...

The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal ...