EXPAREL for Postoperative Pain

Recruiting at 3 trial locations

Overseen By Sarah Shaffer

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Pacira Pharmaceuticals, Inc

Must not be taking: Opioids, Amide anesthetics

Disqualifiers: Coagulopathies, Immunodeficiency, Pre-term birth, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and breakdown of a new pain relief treatment, EXPAREL (bupivacaine extended-release liposome injection), compared to bupivacaine, after heart surgeries in young children. It targets kids under 6 years old who are preparing for heart surgery and will use local anesthesia (pain relief applied directly to the area). The trial will compare two groups: one receiving EXPAREL and the other receiving bupivacaine. Children with a history of allergic reactions to similar medications should not participate.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it does exclude those who have taken EXPAREL or bupivacaine HCl within 30 days before the study. It's best to discuss your current medications with the study team.

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

Research has shown that EXPAREL, a special form of the pain reliever bupivacaine, is generally safe and well-tolerated. One study found that a single dose of 300 mg of EXPAREL was safe for patients, with only minor side effects. Another study demonstrated that EXPAREL effectively reduced pain after surgery, indicating it works well without causing major issues.

While this trial focuses on young children, EXPAREL has been safely used in adults for various surgeries. This provides some confidence in its safety, although data collection is ongoing specifically for young children undergoing heart surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for postoperative pain, which typically involves traditional analgesics like bupivacaine, EXPAREL offers a unique approach by using a long-acting, non-opioid formulation of bupivacaine. Researchers are excited about EXPAREL because it delivers pain relief over an extended period with a single dose, potentially reducing the need for additional pain medication and decreasing reliance on opioids, which have significant side effects and addiction risks. This innovative delivery method allows for sustained pain control, which can enhance patient recovery and comfort after surgery.

What evidence suggests that EXPAREL might be an effective treatment for postoperative pain in pediatric cardiac surgery?

Research has shown that EXPAREL, a type of pain medication, can help reduce pain after surgery. In this trial, participants will receive either EXPAREL or bupivacaine. One study found that patients using EXPAREL reported less pain compared to those using bupivacaine HCl, with scores of 283 versus 329. Another study demonstrated that EXPAREL significantly reduced pain over 72 hours and decreased the need for opioid painkillers. However, some research found that EXPAREL did not provide better pain relief than other treatments in certain cases. Overall, EXPAREL shows promise for managing post-surgery pain, but results can vary. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children aged 0 to less than 6 years undergoing cardiac surgery. Their guardians must understand the consent form and agree to follow the study's schedule. Children should be healthy enough for anesthesia (ASA Class 1-3). Different age groups will be studied in separate parts of the trial.

Inclusion Criteria

Parent/guardian able to speak, read, and understand the language of the ICF and provide informed consent for the subject

American Society of Anesthesiologists (ASA) Class 1-3

Male or female subjects from 0 to less than 6 years of age on the day of surgery. For Part 1, the subject's age should be 2 years to less than 6 years. For Part 2, the subject's age should be 6 months to less than 2 years. For Part 3, the subject's age should be 0 to less than 6 months

Exclusion Criteria

I have a history of blood clotting or immune system disorders.

History of pre-term birth (babies born before 37 weeks of pregnancy)

Clinically significant medical or psychiatric disease that, in the opinion of the investigator, indicates an increased vulnerability to study drugs and/or procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1 Treatment

Subjects aged 2 to less than 6 years receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Part 2 Treatment

Subjects aged 6 months to less than 2 years receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Part 3 Treatment

Subjects aged 0 to less than 6 months receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• bupivacaine
• EXPAREL

Trial Overview The study compares EXPAREL, a long-lasting pain reliever, with bupivacaine, a common local anesthetic, in young patients after heart surgery. It aims to see how these drugs are processed by the body and how safe they are when used for pain control.

How Is the Trial Designed?

Group I: EXPAREL Experimental Treatment 1 Intervention

A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive EXPAREL

Group II: bupivacaine Active Control 1 Intervention

A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive bupivacaine

EXPAREL is already approved in United States for the following indications:

Approved in United States as Exparel for:

• Postsurgical local analgesia via infiltration in patients aged 6 years and older
• Postsurgical regional analgesia in adults via interscalene brachial plexus nerve block

Who Is Running the Clinical Trial?

Pacira Pharmaceuticals, Inc

Lead 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

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]

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]

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 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]

DepoFoam bupivacaine, an extended-release formulation of the local anesthetic bupivacaine, provides effective pain relief for 3-4 days after a single administration at the surgical site, reducing the need for opioid pain relief.

The safety profile of DepoFoam bupivacaine is comparable to traditional bupivacaine HCl, with adverse events being dose-related, indicating it is a safe option for managing postsurgical pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. Bergese, SD., Onel, E., Portillo, J.[2014]

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 phase 3 study involving 189 patients undergoing hemorrhoidectomy, bupivacaine extended-release significantly reduced pain intensity scores compared to placebo, indicating its efficacy in providing long-lasting postoperative analgesia.

Patients receiving bupivacaine extended-release were more likely to remain opioid-free for longer periods and reported higher satisfaction with pain management, highlighting its potential to reduce opioid consumption after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Gorfine, SR., Onel, E., Patou, G., et al.[2022]

In a phase 2 study involving 138 patients undergoing total knee arthroplasty, bupivacaine extended-release liposome injection showed no significant changes in ECG parameters, such as QRS and QTcF durations, indicating a favorable cardiac safety profile.

Across multiple studies with a total of 1459 patients, no clinically relevant cardiac adverse events were associated with bupivacaine extended-release, suggesting it is safe for use in postsurgical pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile. Bergese, SD., Onel, E., Morren, M., et al.[2019]

Exparel™ (DepoFoam bupivacaine) provides a longer-lasting nerve blockade (240 minutes) compared to standard bupivacaine solutions, which lasted 120 minutes and 210 minutes, indicating its potential for improved pain management.

While Exparel™ showed slightly higher inflammation scores than standard bupivacaine solutions shortly after injection, it had similar myotoxicity levels and no neurotoxicity, suggesting it may be a safe option for local anesthesia, though monitoring for tissue reactions is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multivesicular liposomal bupivacaine at the sciatic nerve. McAlvin, JB., Padera, RF., Shankarappa, SA., et al.[2022]

Citations

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

Liposomal extended-release bupivacaine for postsurgical ... The cumulative pain intensity score was found to be lower in patients using EXPAREL® than in patients using bupivacaine HCl (283 versus 329, P = 0.039). The ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03152877

Efficacy of Extended-Release Liposomal Bupivacaine for ... Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022480421001244

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ... Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs.

4. 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 ...

5. investor.pacira.com investor.pacira.com/news-releases/news-release-details/pacira-pharmaceuticals-inc-announces-results-expareltm-pivotal

Release details Administration of EXPAREL resulted in a statistically significant reduction in pain compared to placebo at all time points, including a 30 percent reduction in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4012190/

Safety of liposome extended-release bupivacaine for ... This study found that administration of DepoFoam bupivacaine at a dose of 300 mg was safe and well tolerated in all patients. The only AE attributed to the ...

7. fda.gov fda.gov/media/111001/download

EXPAREL Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter,.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0363502319314212

Bupivacaine Extended-Release Liposomal Injection ... Pain scores and opioid use were similar during the first 4 postoperative days. Opioid use on day 1 was slightly lower with liposomal bupivacaine.