Exparel Injection for Postoperative Pain

Overseen By Elizabeth A Bradley, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Disqualifiers: Under 18, Pregnant, Nursing

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Immediate postoperative period

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

After surgery to remove the eye, either by enucleation or evisceration, patients have variable levels of pain for several postoperative days. Some patients have almost no discomfort while others require significant amounts of oral narcotics and report pain of 10 out of 10 on a numerical rating scale. The current operative standard is to infiltrate the eye socket with 0.5% bupivacaine during surgery leading to several hours of postoperative analgesia. In 2011, Pacira Pharmaceuticals released a bupivacaine liposomal injectable suspension (Exparel, 1.3%) which offers sustained release of bupivacaine giving postoperative pain control for up to 72 hours. This medication has been used in numerous surgeries including inguinal hernia repair, hemorrhoidectomy, bunionectomy, breast reconstruction, and orthopedic surgery, and the literature reports improved pain control, decreased use of oral opioids, and increased patient satisfaction. There are no reports of the use of Exparel in the ophthalmic literature. The investigators propose a randomized, controlled trial to compare the postoperative pain control offered by sustained release bupivacaine to that offered by standard plain bupivacaine after enucleation or evisceration.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Exparel Injection safe for humans?

Exparel, a form of bupivacaine, has been shown to be generally safe in humans when used as directed. Studies indicate minimal side effects when used for pain relief in surgeries, and it is approved by the FDA for surgical infiltration anesthesia. ^{1 2 3 4 5}

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

Exparel is unique because it is a liposomal bupivacaine, which means it is a slow-release form of the local anesthetic bupivacaine, allowing for extended pain relief with a single injection at the surgical site. This can reduce the need for opioids and provide longer-lasting pain control compared to traditional bupivacaine formulations. ^{2 6 7 8 9}

What data supports the effectiveness of the drug Exparel Injection for postoperative pain?

Research shows that Exparel, a form of bupivacaine, can significantly reduce postoperative pain and the need for opioids in various surgeries, such as knee and hip replacements. Studies also indicate that it provides extended pain relief for up to several days after surgery. ^{1 2 3 6 8}

Who Is on the Research Team?

Elizabeth Bradley, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adult patients at Mayo Clinic Rochester undergoing eye removal surgery (enucleation or evisceration) who can understand and use a numerical rating scale to report pain, nausea, and satisfaction. It's not for those under 18 years old or pregnant/nursing individuals.

Inclusion Criteria

I am having my eye removed at Mayo Clinic Rochester by the Ophthalmology Department.

Willing and able to comprehend a numerical rating scale system and provide a score to assess pain, nausea, and satisfaction level.

Exclusion Criteria

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Intraoperative injection of local anesthetic agent, either standard plain bupivacaine or sustained release bupivacaine (Exparel)

Immediate postoperative period

1 visit (in-person, during surgery)

Postoperative Monitoring

Assessment of postoperative pain, nausea, vomiting, and patient satisfaction on day 3 post-surgery

3 days

1 visit (in-person or virtual)

Follow-up

Participants are monitored for postoperative complications and overall recovery

6-8 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine

Trial Overview The study tests if Exparel, a long-lasting bupivacaine suspension providing up to 72 hours of pain control, is more effective than the standard bupivacaine used during eye socket surgeries in reducing postoperative pain.

How Is the Trial Designed?

Group I: Exparel (sustained release bupivacaine) Experimental Treatment 1 Intervention

Intraoperative injection of local anesthetic agent, long acting agent

Group II: Plain bupivacaine Active Control 1 Intervention

Intraoperative injection of local anesthetic agent, standard of care

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study of 37 patients undergoing breast reduction surgery, the use of the long-acting local anesthetic bupivacaine (Sensorcaine) significantly reduced the time to discharge from the postanesthesia care unit, averaging 2.9 hours compared to 3.8 hours for the placebo group.

Patients who received Sensorcaine reported lower pain levels and required significantly less narcotic medication post-surgery, taking an average of 3.5 tablets compared to 6.4 tablets in the control group, indicating its efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Sensorcaine significantly improves postoperative pain management in outpatient reduction mammaplasty. Culliford, AT., Spector, JA., Flores, RL., et al.[2021]

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 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]

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]

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

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 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]

EXPAREL® (bupivacaine liposome injectable suspension) is an effective extended-release local anesthetic that can significantly improve postoperative pain management in orthopedic trauma surgery, as demonstrated in two case studies.

Both patients treated with EXPAREL® experienced good control of postsurgical pain, highlighting its safety and efficacy as part of a multimodal analgesia approach in reducing the risk of chronic pain after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. Hutchinson, HL.[2022]

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]

Citations

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

Intraoperative Sensorcaine significantly improves postoperative pain management in outpatient reduction mammaplasty. [2021]

2. 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]

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

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

5. France pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. [2013]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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