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

Trial Summary

What is the purpose of this trial?

This trial is testing a long-lasting numbing injection called Exparel to help manage pain in teenagers after ACL surgery. The goal is to see if this injection can reduce the need for strong painkillers at home. By using Exparel, doctors hope to lower the risk of opioid misuse among young athletes.

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.

What data supports the effectiveness of the drug Exparel for pain after ACL surgery?

Exparel, a long-acting local anesthetic, has been shown to effectively reduce pain and opioid use in various surgeries, including orthopedic procedures, by providing extended pain relief when used 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 in various surgical settings, including orthopedic trauma and breast augmentation. However, it can have side effects that may lead to emergency department visits, especially when used in certain nerve blocks. ^{1 3 6 7 8}

How is the drug Exparel different from other pain treatments after ACL surgery?

Exparel is unique because it is an extended-release local anesthetic that can be injected directly into the surgical site, providing pain relief for up to 72 hours, which reduces the need for opioids and enhances recovery. ^{1 2 3 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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 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) 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]

References

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

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

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

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

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

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

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

Efficacy of Periarticular Injection With a Long-Acting Local Analgesic in Joint Arthroplasty. [2015]

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

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. [2019]

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

Risk factors for complications and return to the emergency department after interscalene block using liposomal bupivacaine for shoulder surgery. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

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