Exparel vs. Marcaine for Postoperative Pain After Heart Surgery

Overseen By Russell J Pepe, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Pain medications

Disqualifiers: Non-English speaking, Active infection, 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: 2

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this pilot study is to describe and compare Ultrasound-Guided Erector Spinae Plane (ESP) Blocks using Exparel® (bupivacaine liposome injectable suspension) to Marcaine® (bupivacaine hydrochloride) for pain management and outcomes after cardiac surgeries.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently on pain medication for a chronic pain condition.

What data supports the effectiveness of the drug Exparel for postoperative pain after heart surgery?

Research shows that Exparel, a slow-release form of bupivacaine, can extend pain relief for several days after surgery. In a study on cardiac surgery, Exparel was tested for its ability to control pain and reduce the need for opioids, although results were mixed. ^{1 2 3 4 5}

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

Exparel, a long-acting form of bupivacaine, has been shown to be safe in various surgeries, including breast augmentation and peripheral nerve blocks. It is approved for single-dose use to manage pain after surgery, and studies have generally supported its safety profile. ^{1 2 4 5 6}

How does the drug Exparel differ from Marcaine for postoperative pain after heart surgery?

Exparel is a liposomal bupivacaine formulation that provides extended-release pain relief, potentially reducing the need for opioids after surgery. Unlike Marcaine, which is a standard bupivacaine hydrochloride, Exparel is designed for a single-dose application that can offer prolonged pain control. ^{1 3 4 7 8}

Research Team

Leonard Y Lee, MD

Principal Investigator

Rutgers Robert Wood Johnson Medical School, Dept of Surgery

Eligibility Criteria

This trial is for adults of any age who are scheduled for certain heart surgeries like valve repair or bypass graft at a specific academic medical center. It's not suitable for people outside this setting.

Inclusion Criteria

I am 18 years old or older.

I am scheduled for a chest surgery at a specific academic medical center.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative

Administration of ultrasound-guided erector spinae plane (ESP) blocks using Exparel or Marcaine prior to cardiac surgery

Immediate pre-surgery

1 visit (in-person)

Postoperative Monitoring

Monitoring of postoperative opioid and non-opioid analgesic consumption, pain scores, and other outcomes

5 days

Daily monitoring (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including outpatient pain scores and quality of life assessments

30 days

1 visit (in-person)

Treatment Details

Interventions

• Exparel
• Marcaine

Trial Overview The study compares two pain management drugs after heart surgery: Exparel (a long-acting form of bupivacaine) and Marcaine (a standard form), both administered via an ultrasound-guided Erector Spinae Plane Block.

Participant Groups

Group I: Exparel Experimental Treatment 1 Intervention

The experimental medication (Exparel) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project the investigators anticipate consenting 120 subjects to obtain 96 evaluable subjects; 48 Mini thoractomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine).

Group II: Marcaine Active Control 1 Intervention

The active comparator medication (Marcaine) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project the investigators anticipate consenting 120 subjects to obtain 96 evaluable subjects; 48 Mini thoracotomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine).

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Pacira Pharmaceuticals, Inc

Industry Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

Findings from Research

Patients receiving bupivacaine liposome (Exparel) reported significantly lower pain levels and consumed fewer opioid pills on the day of surgery compared to those receiving standard bupivacaine (Marcaine).

However, the benefits of Exparel in reducing pain and opioid use were not sustained beyond the day of surgery, as no significant differences were observed in pain levels or total opioid consumption in the following days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Randomized Study Comparing Bupivacaine Hydrochloride Versus Bupivacaine Liposome for Pain Management After Distal Radius Fracture Repair Surgery. Alter, TH., Liss, FE., Ilyas, AM.[2018]

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 79 patients undergoing cardiac surgery, Exparel, when used as a single-dose parasternal nerve block, showed a marginal decrease in overall postoperative pain levels compared to a placebo, but this difference was not significant at individual time points.

Exparel did not demonstrate any opioid-sparing benefits or improvements in secondary outcomes such as length of hospital stay or recovery times, suggesting it may not be a superior option for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy. Lee, CY., Robinson, DA., Johnson, CA., et al.[2019]

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 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 of 34 patients undergoing breast augmentation, liposomal bupivacaine provided statistically significant lower pain scores compared to standard bupivacaine at multiple time points post-surgery, indicating it may offer better pain control.

Despite the statistical significance, the differences in pain relief were small, and 70% of patients felt the additional cost of liposomal bupivacaine was not justified by the benefits, suggesting limited clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Nadeau, MH., Saraswat, A., Vasko, A., et al.[2022]

In a study of 20 patients undergoing lingual nerve microsurgery, those who received liposomal bupivacaine (LB) reported significantly less postoperative pain and consumed fewer opioid pills compared to those who received bupivacaine hydrochloride (BH).

The findings suggest that LB, with its prolonged duration of action, is more effective in reducing postoperative pain and opioid consumption, supporting its use in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine use in exploratory lingual nerve microsurgery: does liposomal bupivacaine use decrease postoperative pain and opioid consumption compared to bupivacaine hydrochloride? A pilot study. Jacobus, D., Mehr, S., Ziccardi, V.[2021]

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

A Prospective Randomized Study Comparing Bupivacaine Hydrochloride Versus Bupivacaine Liposome for Pain Management After Distal Radius Fracture Repair Surgery. [2018]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy. [2019]

4. 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]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine use in exploratory lingual nerve microsurgery: does liposomal bupivacaine use decrease postoperative pain and opioid consumption compared to bupivacaine hydrochloride? A pilot study. [2021]

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

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