Liposomal Bupivacaine for Cleft Lip and Palate

Overseen By Benjamin M. Smith, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Kerry O'Rourke

Disqualifiers: Under age 6, Cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 5 days

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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 Liposomal Bupivacaine (Exparel) for cleft lip and palate surgery?

Research shows that Liposomal Bupivacaine (Exparel) is effective in reducing postoperative pain and the need for opioids in various surgeries, such as pharyngoplasty and total knee arthroplasty, by providing long-lasting pain relief. ^{1 2 3 4 5}

Is liposomal bupivacaine safe for use in humans?

Liposomal bupivacaine (Exparel) has been shown to be safe in various surgical settings, including breast augmentation and pediatric pharyngoplasty, and is approved by the FDA for use in surgical site pain management. ^{1 2 3 4 6}

How is the drug Liposomal Bupivacaine unique for treating cleft lip and palate?

Liposomal Bupivacaine is unique because it is a long-acting local anesthetic that provides extended pain relief after surgery, reducing the need for additional pain medications. It is delivered in a special formulation that releases the drug slowly over time, which is different from standard anesthetics that require more frequent dosing. ^{1 2 3 5 7}

What is the purpose of this trial?

The goal of this clinical trial is to learn if a pain medication called liposomal bupivacaine (brand name EXPAREL®) with epinephrine will provide better pain control, increased activity, and reduced use of opioids compared with the standard treatment for patients age 6 years and older with cleft lip and palate who have had an alveolar bone graft surgery. Investigators will look at: * pain scores at hip and jaw sites * opioid use in amount and frequency * scores on activity questionnaires Researchers will compare the results of these items with those of patients who had the standard treatment of bupivacaine with epinephrine.

Research Team

Chad A. Purnell, MD

Principal Investigator

Shriners Hospitals for Children

Eligibility Criteria

This trial is for individuals aged 6 and older with cleft lip or palate who are scheduled for alveolar bone graft surgery. It's not suitable for those under age 6, anyone allergic to the study drugs (EXPAREL®, Epinephrine, Bupivacaine), or patients with a history of cardiovascular disease.

Inclusion Criteria

I am 6 or older with a cleft lip/palate and have surgery planned for a bone graft.

Exclusion Criteria

I am older than 6 years old.

I have no allergies to EXPAREL, Epinephrine, or Bupivacaine.

I have a history of heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo alveolar bone graft surgery and receive either liposomal bupivacaine with epinephrine or standard bupivacaine with epinephrine for pain management

5 days

In-patient stay for surgery and immediate post-operative care

Follow-up

Participants are monitored for pain scores, opioid use, and activity levels through questionnaires

5 days

Daily monitoring via paper, electronic, or phone questionnaires

Treatment Details

Interventions

• Liposomal Bupivacaine

Trial Overview The trial is testing if liposomal bupivacaine combined with epinephrine provides better pain control and reduces opioid use after alveolar bone graft surgery compared to standard treatment. Pain levels, opioid consumption, and activity will be measured and compared.

Participant Groups

Group I: LB Treatment Arm Experimental Treatment 2 Interventions

Patients on the treatment arm will receive liposomal bupivacaine mixed with epinephrine (ratio of 1:100,000), which is not considered the standard of care.

Group II: Bupivacaine Control Arm Active Control 2 Interventions

Patients on the control arm will follow the current standard of care, which is traditional bupivacaine mixed with epinephrine (1:100,000).

Liposomal Bupivacaine is already approved in United States for the following indications:

Approved in United States as EXPAREL for:

• Postsurgical local analgesia via infiltration in adults
• Regional analgesia via interscalene brachial plexus nerve block in adults

Who Is Running the Clinical Trial?

Kerry O'Rourke

Lead Sponsor

Trials

1

Recruited

60+

Shriners Hospitals for Children

Collaborator

Trials

98

Recruited

23,900+

Findings from Research

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]

Liposomal bupivacaine (LB) is safe for use in pediatric patients and significantly improves pain control after pharyngoplasty, as evidenced by lower pain scores compared to those receiving standard lidocaine.

Patients treated with LB had earlier oral intake, required fewer opioids, and were discharged from the hospital nearly 2 days earlier than those in the control group, highlighting its efficacy in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. Day, KM., Nair, NM., Griner, D., et al.[2018]

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]

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 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]

Liposomal bupivacaine (LB) was safely used in 27 pediatric patients undergoing palatoplasty, resulting in low postoperative pain scores and reduced opioid consumption, with an average hospital stay of just over 2 days.

Patients tolerated oral intake within approximately 10 hours post-surgery, indicating effective pain management with LB, which may lead to quicker recovery and discharge times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Palatoplasty. Day, KM., Nair, NM., Sargent, LA.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. [2018]

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

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial. [2017]

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. 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

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Palatoplasty. [2022]