Exparel for Postoperative Pain

Overseen By Anna Wilhelmy, MS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Texas Scottish Rite Hospital for Children

Disqualifiers: Fracture repair, Arthrotomy, Pregnancy, 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

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Exparel (bupivacaine liposome injectable suspension), combined with Marcaine, can better manage pain and reduce the need for narcotics after surgery to repair the medial patellofemoral ligament (MPFL) in young athletes. Researchers aim to determine if Exparel reduces pain and the number of pain pills needed in the week following surgery. Participants will receive either Exparel with Marcaine or just Marcaine during their surgery and will report their pain experiences through questionnaires. This trial may suit individuals aged 13 or older who require isolated MPFL reconstruction and can provide consent through a legal representative if necessary. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the focus is on pain management after surgery, it's best to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that Exparel, a long-lasting, non-opioid pain reliever, is safe for patients aged 6 and older, making it a suitable option for children undergoing surgeries like the one in this trial. One study found that patients using Exparel experienced less pain compared to those using another pain reliever, bupivacaine HCl.

Regarding safety, another study examined side effects in children who received Exparel and found no major treatment-related problems. This suggests that Exparel is generally well-tolerated in children undergoing surgery. However, some research indicates that Exparel does not always provide superior pain relief compared to other treatments.

Overall, Exparel appears to be a safe choice for managing post-surgical pain, with the added benefit of reducing the need for opioids. It is important to discuss any concerns with healthcare providers when considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for postoperative pain, which often involves traditional local anesthetics like Marcaine, Exparel offers a unique approach by using a liposomal delivery system. This system allows for a slow and steady release of the active ingredient, bupivacaine, potentially providing longer-lasting pain relief with a single dose. Researchers are excited about Exparel because it could reduce the need for additional doses and reliance on opioids, making recovery more comfortable and safer for patients.

What evidence suggests that Exparel might be an effective treatment for postoperative pain?

Research has shown that Exparel, a type of pain relief medication, has produced mixed results in managing post-surgical pain. Some studies found that Exparel did not significantly ease pain or reduce the need for other painkillers compared to other options. However, evidence presented at medical conferences suggests that patients using Exparel reported low pain levels and were very satisfied with their pain management. In this trial, participants will be assigned to either the Exparel + Marcaine Group or the Marcaine Only Group. Despite these mixed findings, Exparel is designed to release pain relief slowly over time, potentially reducing the need for extra pain medications. Individuals considering this treatment should consider these varied results when deciding whether to join a clinical trial. ^{4 6 7 8 9}

Who Is on the Research Team?

Philip Wilson, MD

Principal Investigator

Texas Scottish Rite Hospital for Children

Are You a Good Fit for This Trial?

This trial is for pediatric patients undergoing surgery to reconstruct the medial patellofemoral ligament (MPFL) due to kneecap dislocations or sports injuries. Participants should not have used any other pain management drugs that could affect the study's results.

Inclusion Criteria

Parent/patient must be fluent in English

I am over 10 years old and need surgery for a specific knee injury.

Exclusion Criteria

I need surgery for a fracture or another specific injury.

I am under 10 years old.

I need or had a specific knee ligament surgery involving bone work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Participants receive pre-operative medications including midazolam and Emend if necessary

1 day

Intra-operative

Participants undergo MPFL reconstruction surgery with either Exparel + Marcaine or Marcaine only

1 day

Post-operative

Participants receive post-operative pain management and complete questionnaires on days 1, 4, and 7

1 week

3 visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exparel

Trial Overview The trial tests if Exparel, when used with Marcaine during MPFL reconstruction surgery, provides better pain relief and reduces narcotic use compared to using Marcaine alone. Pain levels and narcotic consumption are monitored up to one week post-surgery.

How Is the Trial Designed?

Group I: Exparel + Marcaine Group Active Control 1 Intervention

Local Infiltration: Regardless of weight: 10 mL Exparel and 10 mL 0.25% Marcaine

Group II: Marcaine Only Group Active Control 1 Intervention

Local Infiltration: Regardless of weight: 20 mL 0.25% Marcaine

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 via an interscalene brachial plexus block in adults
• Postsurgical regional analgesia via a sciatic nerve block in the popliteal fossa in adults
• Postsurgical regional analgesia via an adductor canal block in adults

Who Is Running the Clinical Trial?

Texas Scottish Rite Hospital for Children

Lead Sponsor

Trials

23

Recruited

9,000+

Published Research Related to This Trial

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]

Liposomal bupivacaine (Exparel) has been shown to be a safe and effective option for managing postoperative pain in plastic surgery, based on a review of eight studies involving 405 patients.

Compared to traditional pain management methods, liposomal bupivacaine was found to be equivalent or more effective, suggesting it could serve as a less invasive alternative to more complex pain management systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. Vyas, KS., Rajendran, S., Morrison, SD., 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 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28478185/

Effectiveness of Bupivacaine Liposome Injectable ... Conclusion: There is no benefit in the use of liposomal bupivacaine compared with ropivacaine for postoperative pain control in TKA.

2. 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.

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2790975

Efficacy of Liposomal Bupivacaine and ... This study found that liposomal bupivacaine did not improve postoperative recovery or pain compared with bupivacaine hydrochloride alone among patients ...

4. investor.pacira.com investor.pacira.com/news-releases/news-release-details/new-data-support-benefits-exparel-postsurgical-analgesia

New Data Support the Benefits of EXPAREL for ... Results Presented at American Society for Aesthetic Plastic Surgery Meeting Show Patients Treated with EXPAREL Reported Low Pain Scores, High Satisfaction ...

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

EXPAREL (bupivacaine liposome injectable suspension) The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration were pyrexia, dizziness, edema peripheral ...

6. exparel.com exparel.com/

Postsurgical Pain Relief | EXPAREL® (bupivacaine liposome ... EXPAREL (bupivacaine liposome injectable suspension) is indicated to produce postsurgical local analgesia via infiltration in patients aged 6 years and older.

7. 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 ...

8. fda.gov fda.gov/media/111001/download

EXPAREL EXPAREL. ®. (bupivacaine liposome injectable suspension) is a long-acting, non-opioid analgesic. Bupivacaine, the active pharmaceutical ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30521078/

Incidence of adverse events attributable to bupivacaine ... The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal ...