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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, Exparel (bupivacaine liposome injectable suspension) and Marcaine, to determine which better manages pain after heart surgery. The focus is on the ESP block technique, where medication is delivered near the spine to control pain. The study seeks adults scheduled for specific heart surgeries, such as valve repair or bypass graft, who are not currently using pain medication for a chronic condition. The goal is to enhance pain relief and recovery outcomes for these patients. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancements in pain management.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Exparel, a type of bupivacaine, is generally safe for people. Studies have found that it can relieve pain for up to 72 hours after surgery. It is approved for use as a one-time treatment to manage post-surgical pain. Side effects are rare, affecting less than 2% of patients, and may include chills, slow heart rate, and anxiety.

Marcaine, another form of bupivacaine, is well-known and widely used for pain relief. It has been safely used in many medical procedures for a long time. Side effects can occur but are usually mild, such as dizziness and nausea.

Research indicates that both treatments are well-tolerated. This information may help prospective trial participants feel more confident about the safety of these medications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for postoperative pain after heart surgery, which often include traditional analgesics like opioids or local anesthetics such as lidocaine, Exparel and Marcaine offer unique advantages. Exparel is exciting because it uses a long-acting formulation of bupivacaine, delivered through a special DepoFoam technology that releases the medication over time, potentially providing pain relief for up to 72 hours with a single dose. Marcaine, another form of bupivacaine, is used routinely but typically has a shorter duration of action. Researchers are interested in seeing if Exparel's extended-release formulation can offer improved pain control and reduce the need for additional pain medications after surgery.

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

This trial compares Exparel, a special form of the pain reliever bupivacaine, to Marcaine for managing postoperative pain after heart surgery. Research has shown that Exparel can provide longer-lasting pain relief, reducing pain for up to 72 hours after the procedure. Some studies found that Exparel can lead to slightly lower pain levels compared to regular bupivacaine in certain surgeries. Meanwhile, Marcaine, the standard form of bupivacaine, is widely used and effective for managing post-surgery pain. Both treatments in this trial aim to lessen the need for additional pain medication, with Exparel's longer-lasting effect potentially offering benefits for extended pain management. ^{3 4 6 7 8}

Who Is on the Research Team?

Leonard Y Lee, MD

Principal Investigator

Rutgers Robert Wood Johnson Medical School, Dept of Surgery

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003497518311676

A Randomized Controlled Trial of Liposomal Bupivacaine ... Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851 .)

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3772762/

Liposomal extended-release bupivacaine for postsurgical ... The double-blinded study found that the cumulative pain intensity scores through 4 days postsurgery were 20.7, 19.5, 18.8, and 19.1, for using EXPAREL® at doses ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7967071/

Effectiveness of Standard Local Anesthetic Bupivacaine and ... This randomized clinical trial investigates the effectiveness of liposomal bupivacaine vs standard bupivacaine for postoperative pain in patients with truncal ...

4. annalsthoracicsurgery.org annalsthoracicsurgery.org/article/S0003-4975(18)31167-6/fulltext

A Randomized Controlled Trial of Liposomal Bupivacaine ... This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02969187

Bupivacaine Liposomal Injection (Exparel) for Postsurgical ... Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for longer postoperative period analgesic. It provides up to 72 hours analgesia ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11975001/

Real-World Pharmacovigilance Analysis of Adverse Events ... This study analyzed adverse events (AEs) associated with liposomal bupivacaine and bupivacaine using the FDA Adverse Event Reporting System (FAERS) database

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf

EXPAREL (bupivacaine liposome injectable suspension) The less common/rare adverse reactions (incidence less than 2%) following EXPAREL administration were chills, erythema, bradycardia, anxiety, urinary retention, ...

8. aetna.com aetna.com/cpb/medical/data/900_999/0941.html

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ... The authors concluded that bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid ...