Exparel vs Bupivacaine for Postoperative Pain After Thoracoscopy

Overseen By Christopher Cowart, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Narcotics

Disqualifiers: Pregnancy, Liver dysfunction, Dementia, 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

Compensation: Varies

Number of Visits: 4

Duration: Immediate (intraoperative)

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to manage pain after minimally invasive chest surgeries. It compares two treatments: Exparel, a long-lasting pain reliever, and regular Bupivacaine (also known as Marcaine or Sensorcaine), to determine which better controls pain and reduces opioid use. The trial targets individuals undergoing specific thoracoscopic surgeries, such as VATS lobectomies, who are not already on strong pain medications or have certain health conditions. The goal is to enhance comfort and recovery after surgery, potentially leading to shorter hospital stays and fewer complications. As a Phase 4 trial, it involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking narcotics for chronic pain near the surgical site, you may be excluded from participating.

What is the safety track record for Exparel and Bupivacaine?

Research has shown that Exparel, a type of pain medication, is generally safe and well-tolerated for managing post-surgical pain. Common side effects, such as fever, dizziness, and swelling, occur in less than 10% of patients. Studies have found that Exparel effectively relieves pain for up to 72 hours after surgery and may reduce the need for opioids, which carry their own risks.

Safety data also supports the use of regular bupivacaine, particularly for post-surgical pain control. It has been used as a local anesthetic for a long time and carries a low risk of serious side effects when administered in appropriate amounts. However, both Exparel and regular bupivacaine require close monitoring to ensure safe blood levels, as high levels can cause serious nervous system or heart problems.

Overall, both treatments have a strong safety record when used correctly and can effectively manage pain after surgeries like thoracoscopy. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Exparel for postoperative pain after thoracoscopy because it offers prolonged pain relief with a single dose. Unlike standard treatments like traditional bupivacaine, which typically lasts only a few hours, Exparel is a long-acting formulation that can provide pain control for up to 72 hours. This extended duration is achieved through its unique delivery system using liposome technology, which slowly releases the anesthetic over time. This means fewer doses and potentially less reliance on opioids, making recovery smoother and safer for patients.

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

This trial will compare Exparel with Bupivacaine for postoperative pain management after thoracoscopy. Research has shown that liposomal bupivacaine (Exparel) does not provide better pain relief than regular bupivacaine or other local painkillers in chest surgeries. Specifically, studies found that Exparel did not significantly lower pain or reduce the need for opioids after surgery compared to traditional bupivacaine. In most studies, Exparel was not more effective at managing pain or aiding recovery. Therefore, current evidence suggests that Exparel is not more effective for controlling pain after chest surgeries than standard bupivacaine. ^{6 7 8 9 10}

Who Is on the Research Team?

Zoulfira Nisnevitch-Savarese, MD

Principal Investigator

Penn State Hershey College of Medicine

Are You a Good Fit for This Trial?

Adults over 18 undergoing specific minimally invasive chest surgeries can join this trial. Excluded are those under 18, pregnant or breastfeeding women, patients on preoperative narcotics for chronic pain near the surgery site, non-English speakers, individuals weighing less than 48 kg, and those with dementia, kidney dysfunction, liver issues, allergies to local anesthetics or previous similar surgeries.

Exclusion Criteria

I have liver problems.

My surgeon thinks it's likely my lung surgery might change from a keyhole to an open procedure.

I have had surgery on the same side of my chest before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intercostal injections of either 266 mg of liposomal bupivacaine or 0.5% plain bupivacaine for pain management during and after thoracoscopic surgeries

Immediate (intraoperative)

1 visit (in-person)

Follow-up

Participants are monitored for plasma concentration of bupivacaine and secondary outcomes such as opioid consumption, pain levels, and complications like pneumonia and atrial fibrillation

3 months

Multiple visits (in-person and virtual) over 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Exparel

Trial Overview

The study is testing if liposomal bupivacaine (Exparel) given during chest surgery controls pain as effectively as plain bupivacaine without reaching toxic levels in the blood. It also looks at whether Exparel reduces opioid use and post-surgery pain up to three months later.

How Is the Trial Designed?

Group I: Exparel Experimental Treatment 1 Intervention

Intercostal injection of 266mg of Exparel diluted to 30 ml.

Group II: Bupivacaine Active Control 1 Intervention

Intercostal injection of 0.5% Bupivacaine 2 mg/kg dose diluted to 30 ml.

Bupivacaine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in European Union as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in Canada as Sensorcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

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 100 patients with pulpal necrosis, liposomal bupivacaine did not show a statistically significant improvement in postoperative pain relief compared to standard bupivacaine, with success rates of 29% and 22% respectively.

While liposomal bupivacaine had some effects on soft tissue numbness and non-narcotic medication use, these effects were not clinically significant, indicating that it may not provide additional benefits over traditional bupivacaine for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial. Glenn, B., Drum, M., Reader, A., et al.[2017]

In a study of 85 patients undergoing open thoracotomies, multilevel intercostal nerve blocks using liposomal bupivacaine provided significantly better pain control on postoperative days 1 and 3 compared to traditional epidural analgesia.

The use of intercostal nerve blocks was associated with fewer pulmonary complications and a shorter hospital stay (7.4 days) compared to the epidural group (9.3 days), highlighting its safety and efficacy as a pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operative Intercostal Nerve Blocks With Long-Acting Bupivacaine Liposome for Pain Control After Thoracotomy. Khalil, KG., Boutrous, ML., Irani, AD., 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]

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]

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]

Citations

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Statistical Analysis Plan

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According to this meta-analysis, LB was found to be not superior to non-liposomal local anesthetics for analgesic and functional outcomes in thoracic surgery.

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

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Liposomal bupivacaine vs. Ropivacaine for wound ...

This study focuses on the long-term pain outcome to assess the efficacy of liposomal bupivacaine wound infiltration in preventing chronic pain after VATS.