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

Trial Summary

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

Research shows that Exparel, a slow-release form of bupivacaine, can extend pain relief for several days after surgery. It has been used effectively for pain control in other surgeries, like thoracotomy, where it was used in nerve blocks to manage intense postoperative pain. ^{1 2 3 4 5}

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

Exparel, a slow-release form of bupivacaine, is approved for use in surgical sites to manage pain and has been studied for safety in various applications. Some studies have looked at its use in nerve blocks and other areas, showing it can be safe, but it should be used as approved to avoid potential risks. ^{1 2 3 4 6}

How is the drug Exparel different from other treatments for postoperative pain after thoracoscopy?

Exparel is unique because it is a long-acting form of bupivacaine delivered through a multivesicular liposomal system, allowing for extended pain relief with a single dose. This formulation can reduce the need for additional pain medications and has fewer side effects like hypotension (low blood pressure) and urinary retention compared to traditional epidural analgesia. ^{1 2 5 6 7}

What is the purpose of this trial?

The purpose of this study is to assess pharmacokinetics of liposomal bupivacaine (Exparel) after multilevel intercostal injections of this local anesthetic for pain control during and after thoracoscopic surgeries. The specific aim of this study is to evaluate plasma concentration of bupivacaine after intraoperative intercostal injections of 266 mg of liposomal bupivacaine and compare it to plasma concentrations of bupivacaine after intercostal injections of 2mg/kg of 0.5% plain Bupivacaine with maximal dose of 30 ml or 150 mg. The hypothesis of the study is that plasma concentration of bupivacaine after intercostal injections of 266 mg of liposomal bupivacaine will be similar to concentrations after injections of plain bupivacaine, and will remain below the toxic level threshold range of 2000-3000 ng/mL (2-3 mg/L) at which central nervous system and cardiovascular adverse events would be expected to occur. The secondary objective is to evaluate if intercostal injections of 266 mg of liposomal bupivacaine will significantly reduce opioid consumption and postsurgical pain, within the first 48 hours and up to 3 months after minimally invasive thoracic surgeries, to determine if both acute and chronic post-thoracotomy pain can be decreased by intraoperative intercostal injections of liposomal bupivacaine. Additionally, the rate of pneumonia, the rate of atrial fibrillation and length of hospital stay will be assessed as secondary outcomes after thoracic surgeries. These outcomes can be affected by the level of postoperative pain and inflammation. Significance of this study: If positive, the results of this research have the potential to significantly improve pain management after thoracoscopic surgery. Based on prior experience, prolonged analgesia after liposomal bupivacaine injection is safe, and may help reduce perioperative opioid consumption and decrease opioid related complications. It will improve patient comfort, eliminate need for indwelling neuraxial catheters and risks associated with them.

Research Team

Zoulfira Nisnevitch-Savarese, MD

Principal Investigator

Penn State Hershey College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 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 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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2017]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Operative Intercostal Nerve Blocks With Long-Acting Bupivacaine Liposome for Pain Control After Thoracotomy. [2022]

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

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

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

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