Exparel vs Bupivacaine for Postoperative Pain After Thoracoscopy

Recruiting in Palo Alto (17 mi)

Overseen by Zoulfira Nisnevitch-Savarese, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Narcotics

Disqualifiers: Pregnancy, Liver dysfunction, Dementia, others

No Placebo Group

Prior Safety Data

Trial Summary

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.

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.

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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.

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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.

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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.

Inclusion Criteria

I am over 18 and will have a minimally invasive chest surgery.

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Milton S. Hershey Medical Center Hershey, PA

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center Lead Sponsor

References

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

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022] Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks.

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

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020] Liposomal bupivacaine (Exparel®) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve toxicity and clinical effectiveness of perineural Exparel® alone or with added dexamethasone in a mouse model.

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] Medical studies have shown some potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA), a slow-release bupivacaine solution, to extend postoperative benefits of numbness/pain relief for up to several days. Because the Food and Drug Administration has approved Exparel only for infiltrations, we wanted to evaluate if it would be effective as an infiltration to control postoperative pain. The purpose of this study was to compare an infiltration of bupivacaine with liposomal bupivacaine for postoperative numbness and pain in symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain.

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] An injectable liposomal bupivacaine suspension (EXPAREL™) is approved by the US Food and Drug Administration for analgesia by tissue infiltration and interscalene brachial plexus, but not for use in the neuraxial space. This pilot study describes neurological and histological outcomes of escalating doses of this extended-release formulation of bupivacaine after subarachnoid administration.

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

Operative Intercostal Nerve Blocks With Long-Acting Bupivacaine Liposome for Pain Control After Thoracotomy. [2022] Postthoracotomy pain is quite intense. Epidural analgesia (EPI) has long been the gold standard but is often associated with hypotension and urinary retention. The recent availability of liposomal bupivacaine formulation (Exparel) stimulated us to use it for multilevel intercostal nerve blocks (IB) injected during open thoracotomy.

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

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. [2022] Management of postoperative pain often requires multimodal approaches. Suboptimal dosages of current therapies can leave patients experiencing periods of insufficient analgesia, often requiring rescue therapy. With absence of a validated and standardized approach to pain management, further refinement of treatment protocols and targeted therapeutics is needed. Liposomal bupivacaine (Exparel) is a longer acting form of traditional bupivacaine that delivers the drug by means of a multivesicular liposomal system. The effectiveness of liposomal bupivacaine has not been systematically analyzed relative to conventional treatments in plastic surgery.

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

Recent advances in incorporation of local analgesics in postsurgical pain pathways. [2014] Total knee and hip replacement surgeries are highly invasive, and a significant level of postoperative pain is commonplace in patients undergoing these procedures. It is now known that postoperative pain can affect hospital stay, patient satisfaction, postsurgical rehabilitation, and a range of other clinical and administrative outcomes. The need for a multimodal approach to the control of postoperative pain, using combinations of agents that have synergistic effects, is now widely accepted. There has been increasing interest in local periarticular and intra-articular injections, which can result in significantly less pain in the postanesthesiology care unit (PACU), significantly less use of rescue opioids in the PACU, significantly less confusion, significantly less blood loss, and a significantly lower bleeding index. EXPAREL® (bupivacaine liposome injectable suspension) is an extended-release anesthetic that is approved by the US Food and Drug Administration for single-dose injection into the surgical site to produce postsurgical analgesia. Several phase 2 and phase 3 studies across a range of surgical procedures have demonstrated that the inclusion of EXPAREL® in the multimodal regimen can significantly reduce both pain scores (including cumulative pain scores at 24 hours) and opioid consumption, as well as resulting in delayed time to the first use of opioids and more opioid-free patients at 72 hours. Multimodal regimens that include EXPAREL® may have important benefits in total joint arthroplasty.