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

100 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Exparel for postoperative pain?

Research shows that Exparel, a long-acting form of bupivacaine, can significantly reduce pain scores and the need for opioids after surgery, especially in joint replacement procedures. It is approved for single-dose injection at the surgical site to help manage postsurgical pain. ^{1 2 3 4 5}

Is Exparel (liposomal bupivacaine) safe for use in humans?

Exparel, a long-acting form of bupivacaine, is generally considered safe for use in humans when administered correctly, but it can have side effects that may lead to emergency department visits, especially when used in certain types of nerve blocks. Studies have shown it can cause delayed nerve inflammation in animal models, and its safety profile varies depending on the method of administration. ^{1 2 3 5 6}

What makes Exparel different from other drugs for postoperative pain?

Exparel is unique because it is a long-acting form of bupivacaine delivered through a special liposomal system, allowing for extended pain relief with a single dose directly at the surgical site, unlike traditional bupivacaine which requires more frequent dosing. ^{1 2 3 5 7}

What is the purpose of this trial?

This is a prospective, randomized study to evaluate anaesthetic parameters, postoperative analgesia and oral analgesic consumption comparing exparel (liposomal bupivacaine) vs. standard bupivacaine

Research Team

Faisal Quereshy, MD

Principal Investigator

Case Western Reserve University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Risk factors for complications and return to the emergency department after interscalene block using liposomal bupivacaine for shoulder surgery. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

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