Exparel for Pain After ACL Surgery

Overseen By John Schlechter, DO

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital of Orange County

Disqualifiers: Major surgery, Learning disability, 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: 2

Duration: 1 day

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage pain for young athletes after ACL surgery, aiming to reduce the need for potentially addictive opioids. It compares a standard pain relief method using Bupivacaine with Exparel (bupivacaine liposome injectable suspension), which may offer longer-lasting relief. The goal is to determine if Exparel can reduce narcotic use at home. Children and teenagers who require ACL surgery and have no major learning disabilities or previous major surgeries may qualify for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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

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

Research has shown that Exparel, a long-lasting form of the pain reliever bupivacaine, helps reduce pain after surgery and lessens the need for opioids. In past studies, patients who received Exparel reported less pain and used fewer opioids compared to those who received the regular form of bupivacaine. This suggests that Exparel might effectively manage pain with fewer opioid-related side effects.

Regarding safety, Exparel has generally been well-tolerated. The side effects reported are similar to those of regular bupivacaine and are mostly minor. However, one study noted that the benefits of Exparel for pain control might not be worth it in all situations, indicating that its effectiveness can vary.

Overall, Exparel has shown promise in reducing pain and the need for opioids, with a safety profile similar to standard treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pain after ACL surgery?

Most treatments for pain after ACL surgery, like the standard adductor canal block with bupivacaine, focus on numbing the nerves. But Exparel is unique because it uses bupivacaine in a liposome injectable suspension, which allows for a slower and more controlled release of the medication. This means it could potentially provide longer-lasting pain relief with just one application, reducing the need for additional pain medication and improving patient comfort. Researchers are excited about Exparel because it might enhance recovery by minimizing pain and reducing dependency on opioids.

What evidence suggests that Exparel might be an effective treatment for pain after ACL surgery?

In this trial, participants will receive either Exparel or a standard adductor canal block with bupivacaine. Research has shown that Exparel, a type of pain relief medication, can reduce the need for opioids after surgery. Studies have found that it effectively manages pain without increasing discomfort. This is crucial because using fewer opioids can help prevent addiction, particularly in young athletes. In past trials, Exparel was compared to regular pain relief medications and showed promise in reducing the need for strong painkillers at home after surgeries like ACL reconstruction. These findings suggest that Exparel might lead to better pain control with fewer opioids. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for young athletes with ACL tears who may need surgery and are at risk of opioid misuse. Participants should not have a history of opioid abuse or dependency, and must be able to follow post-surgical care instructions.

Inclusion Criteria

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

Surgery scheduled between the hours of 8am - 4pm

Exclusion Criteria

I have not had any major surgeries like transplants or heart surgery.

Learning disability or developmental delay assessed by an outside specialist and communicated to attending physician or located in patient's medical record

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Data Collection

Participants wear Actigraphs to obtain baseline sleep activity data

1 week

1 visit (in-person)

Treatment

Participants undergo ACL reconstruction with either standard ACB with bupivacaine or Exparel

1 day

1 visit (in-person)

Postoperative Monitoring

Data collected on narcotic consumption, pain levels, functional disability, and anxiety

2 weeks

Daily monitoring (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 study tests if Exparel, an extended-release pain medication, can reduce the need for narcotics after ACL surgery compared to standard Bupivacaine. The goal is to see if Exparel can help manage pain effectively while lowering the risk of opioid use.

How Is the Trial Designed?

Group I: Exparel Experimental Treatment 1 Intervention

Adductor Canal Block with Bupivacaine Liposome Injectable Suspension Admixture bupivacaine 0.5 % 10 cc with Bupivacaine Liposome Injectable Suspension 10cc total 20

Group II: Standard ACB with bupivacaine Active Control 1 Intervention

Standard Adductor Canal Block (ACB) with Bupivacaine Standardized amount of 0.5% bupivacaine 20 cc

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?

Children's Hospital of Orange County

Lead Sponsor

Trials

38

Recruited

5,700+

Published Research Related to This Trial

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 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 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) provides effective pain relief for up to 72 hours after foot and ankle surgeries, making it a valuable option for outpatient procedures.

In two case studies involving complex surgeries, both patients experienced excellent control of postsurgical pain, highlighting the efficacy of EXPAREL® in managing pain without the risks associated with more extensive nerve blocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in foot and ankle surgery: case-based reviews. Herbst, SA.[2014]

In a study involving 59 patients undergoing total knee arthroplasty, liposomal bupivacaine did not show a significant clinical advantage over standard bupivacaine in terms of postoperative recovery, as measured by the number of physical therapy sessions needed for discharge.

The use of liposomal bupivacaine was associated with higher medication charges, raising concerns about its cost-effectiveness compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. Hyland, SJ., Deliberato, DG., Fada, RA., et al.[2019]

In a study of 352 patients undergoing shoulder surgery with an Exparel interscalene block, 16.5% experienced postoperative complications, with 6.0% leading to emergency department visits, highlighting the need for careful patient selection.

The American Society of Anesthesiologists (ASA) score was identified as a significant risk factor for both minor and major complications, suggesting that patients with higher ASA scores may be at greater risk when receiving this type of anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for complications and return to the emergency department after interscalene block using liposomal bupivacaine for shoulder surgery. Malige, A., Yeazell, S., Ng-Pellegrino, A., et al.[2021]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0749806323000361

Postoperative Pain Management After Anterior Cruciate ... Effective analgesia is essential after anterior cruciate ligament (ACL) reconstruction to control pain while minimizing opioid consumption and allowing early ...

2. journalofsurgicalresearch.com journalofsurgicalresearch.com/article/S0022-4804(21)00124-4/abstract

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ... The objective was to assess the efficacy of randomized clinical trials (RCTs) of liposomal bupivacaine in postoperative pain management and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9353693/

Liposomal Bupivacaine Decreases Post-Operative Opioid ... It has been demonstrated that decreasing the strength of opioids given after surgery does not increase pain scores or subsequent opioid ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06274008?term=exparel&viewType=Table&rank=5

Exparel vs. ACB With Bupivacaine for ACL Reconstruction The purpose of the current study is to determine if extended-release Bupivacaine Liposome Injectable Suspension ( Exparel ) is effective in decreasing at home ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06274008/exparel-vs-acb-with-bupivacaine-for-acl-reconstruction

Exparel vs. ACB With Bupivacaine for ACL Reconstruction Exparel vs. ACB With Bupivacaine for ACL Reconstruction ; Phase. 1 ; Condition. Pain. Opioid Use Disorder ; Treatment. Exparel ; Clinical Study ID.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02606448

Exparel Infiltration in Anterior Cruciate Ligament ... The study compares pain control and opioid consumption in patients undergoing ACL reconstruction between patients receiving liposomal bupivacaine and those who ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27159290/

Liposomal Bupivacaine for Pain Control After Anterior ... This study does not support the widespread use of liposomal bupivacaine for pain control after ACL reconstruction in the setting of a femoral nerve block.

8. youthsportsortho.com youthsportsortho.com/pdf/does-liposomal-bupivacaine-injectable-suspension-21.pdf

Does Liposomal Bupivacaine Injectable Suspension This study sought to determine whether liposomal bupivacaine injectable suspension admixture administered as a single-shot adductor canal.