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

100 Participants Needed

Trial Summary

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.

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

Exparel, a long-acting form of bupivacaine, has been shown to provide effective pain relief in orthopedic trauma surgeries, helping patients manage postoperative pain effectively as part of a multimodal pain management approach. ^{1 2 3 4 5}

Is Exparel safe for use in humans?

Exparel, a long-acting form of bupivacaine, has been shown to be safe for use in various surgical procedures, including breast augmentation and orthopedic trauma surgeries, providing effective pain relief with minimal side effects. ^{1 2 3 5 6}

What makes the drug Exparel unique for postoperative pain management?

Exparel is unique because it is an extended-release formulation of bupivacaine, allowing for a single-dose injection directly into the surgical site to provide long-lasting pain relief after surgery. This reduces the need for additional pain medications, including opioids, and is part of a multimodal approach to pain management. ^{1 2 3 5 7}

What is the purpose of this trial?

The goal of this randomized clinical trial is to determine if administration of Exparel via local infiltration for medial patellofemoral ligament (MPFL) reconstruction procedures in pediatric orthopaedic sports medicine patients provides significant pain relief and decreased narcotic use. The main questions it aims to answer are: * Does Exparel significantly reduce Visual Analog Scale (VAS) pain scores and pain levels up to one week postoperatively? * Does Exparel significantly decrease narcotic use (number of pills taken) up to one week postoperatively? Researchers will compare the pain outcomes and narcotic use of patients who receive Exparel and Marcaine via local infiltration to those of patients who receive only Marcaine via local infiltration for their MPFL reconstruction surgery. The goal is to understand if there is a significant difference in patient pain outcomes and narcotic use outside the first 24 hours postoperatively. Participants will: * receive either Exparel + Marcaine intraoperatively or Marcaine only intraoperatively during their MPFL reconstruction surgery * receive and complete questionnaires at postoperative days 1, 4, and 7 regarding their pain scores, levels, and outcomes, effective pain treatments, overall pain interference, narcotic use (number of pills taken), and overall pain treatment satisfaction * receive and complete secondary outcome measures of functional and psychological outcomes regarding their MPFL reconstruction surgery at postoperative day 1

Research Team

Philip Wilson, MD

Principal Investigator

Texas Scottish Rite Hospital for Children

Eligibility Criteria

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 am under 10 years old.

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

I need surgery for a leg injury that isn't just an MPFL repair.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Exparel + Marcaine Group Active Control 1 Intervention

* If \< 40 kg: 4 mg Exparel per kg BW and 30 mL 0.9% normal saline * If 40-70 kg: 10 mL Exparel, 10 mL 0.25% Marcaine, and 10 mL 0.9% normal saline * If \> 70 kg: 20 mL Exparel and 10 mL 0.25% Marcaine

Group II: Marcaine Only Group Active Control 1 Intervention

* If ≤ 20 kg: 1 mL/kg 0.25% Marcaine * If \> 20 - 70 kg: 20 mL 0.25% Marcaine and 10 mL 0.9% normal saline * If \> 70 kg: 30 mL 0.25% Marcaine and 20 mL 0.9% normal saline

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+

Findings from Research

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 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 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]

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 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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019]

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

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. [2022]

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

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. [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. United States pubmed.ncbi.nlm.nih.gov

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