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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pain medication, liposomal bupivacaine, to determine if it provides better pain relief and increases activity while reducing opioid use after surgery for people with cleft lip and palate. Researchers will compare it with the standard pain treatment, bupivacaine, to identify which works better. The trial seeks participants aged 6 years and older who have been diagnosed with cleft lip and/or palate and are scheduled for alveolar bone graft surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially more effective pain management option.

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.

Is there any evidence suggesting that liposomal bupivacaine is likely to be safe for humans?

Research has shown that liposomal bupivacaine is generally safe for surgeries like cleft lip and palate repair. Past studies demonstrated its safe use in children undergoing similar surgeries. The most common side effects were mild, such as nausea and temporary numbness. Serious side effects occurred in about 8% of participants, which is relatively low. This indicates that while some risks exist, liposomal bupivacaine is usually well-tolerated.

Researchers are testing this treatment in a late-stage study, indicating they already have some safety evidence from earlier studies. Additionally, its approval for other types of surgeries supports its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for cleft lip and palate, which involves traditional bupivacaine mixed with epinephrine, liposomal bupivacaine offers a new delivery method. This formulation uses liposomes—tiny fat-like particles—to release the medication slowly, potentially providing longer-lasting pain relief. Researchers are excited about this treatment because it may reduce the frequency of dosing and improve patient comfort post-surgery, offering a significant improvement over current pain management options.

What evidence suggests that liposomal bupivacaine might be an effective treatment for cleft lip and palate?

Research has shown that liposomal bupivacaine (Exparel), which participants in this trial may receive, effectively reduces post-surgical pain and decreases opioid use. Studies have demonstrated its effectiveness in managing pain for patients with cleft lip and palate undergoing surgeries like bone grafting. It is considered a safe option for these procedures, particularly in children. Liposomal bupivacaine offers longer-lasting pain relief compared to traditional bupivacaine, reducing the need for additional medication and aiding recovery. ^{1 2 3 6 7}

Who Is on the Research Team?

Chad A. Purnell, MD

Principal Investigator

Shriners Hospitals for Children

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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) 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40966057/

Safety and Efficacy of Liposomal Bupivacaine (ExparelⓇ) ... Conclusions: Lipsomal bupivacaine appears to be a safe adjunct for postoperative pain management in cleft lip and palate surgery for pediatric ...

2. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10556656251380539

Safety and Efficacy of Liposomal Bupivacaine (ExparelⓇ) ... Conclusions: Lipsomal bupivacaine appears to be a safe adjunct for postoperative pain management in cleft lip and palate surgery for pediatric ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06284434

Liposomal Bupivacaine Use in Alveolar Bone Graft Patients The study will enroll patients with cleft lip and palate undergoing an alveolar bone graft (ABG) surgery. Researchers will enroll a maximum of 60 patients ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38227634/

Liposomal Bupivacaine Use During Orthognathic Surgery ... This study explores the efficacy of liposomal bupivacaine for postoperative pain management in adolescent CLP patients undergoing orthognathic surgery.

5. withpower.com withpower.com/trial/liposomal-bupivacaine-for-cleft-lip-and-palate-89c60

Liposomal Bupivacaine for Cleft Lip and Palate Research shows that Liposomal Bupivacaine (Exparel) is effective in reducing postoperative pain and the need for opioids in various surgeries, such as ...

6. journals.lww.com journals.lww.com/prsgo/fulltext/2021/01000/is_the_use_of_opioids_safe_after_primary_cleft.25.aspx

Is the Use of Opioids Safe after Primary Cleft Palate Repair In this study, we performed a systematic review to evaluate the safety of opioid use to manage postoperative pain following a primary cleft palate repair.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1748681519304292

Retrospective cohort-based comparison of intraoperative ... Liposomal bupivacaine (LB) has been demonstrated to provide improvement in postoperative pain for patients undergoing bunionectomy or hemorrhoidectomy, which ...