Exparel for Craniofacial Pain

Recruiting at1 trial location

Overseen by Peter Hwang, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Disqualifiers: Age <18 or >80, Pregnancy, Allergy to bupivacaine, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if injecting Exparel into the nasal area can help people with craniofacial pain. Exparel is a long-lasting pain reliever, and the study focuses on those who usually get pain relief from Lidocaine during ENT procedures.

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 (Bupivacaine Liposome) for craniofacial pain?

Exparel, a long-acting form of the local anesthetic bupivacaine, has been shown to effectively reduce postoperative pain and the need for opioid painkillers in various surgical procedures, such as orthopedic surgeries. This suggests it may also help manage craniofacial pain by providing extended pain relief. ^{1 2 3 4 5}

Is Exparel (Bupivacaine Liposome) generally safe for use in humans?

Exparel (Bupivacaine Liposome) has a safety profile similar to regular bupivacaine, with some inflammation and muscle damage observed in animal studies, but no nerve damage was detected. In humans, adverse effects are dose-related, and it has been used safely in various surgical procedures, though monitoring for local tissue injury is important. ^{1 2 3 6 7}

How is the drug Exparel different from other treatments for craniofacial pain?

Exparel is unique because it uses a liposome (tiny fat-like particles) to slowly release bupivacaine, a local anesthetic, over time, providing longer-lasting pain relief compared to traditional bupivacaine injections. ^{8 9 10 11 12}

Research Team

Peter Hwang, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults aged 18-80 with craniofacial pain conditions like migraines and cluster headaches, who visit Stanford Pain & ENT clinic. It's not for pregnant women, those with bupivacaine allergies, or anyone unable to consent or afford treatment.

Inclusion Criteria

I have severe head or facial pain and have seen a specialist at the Stanford Pain & ENT clinic.

Exclusion Criteria

You are allergic to bupivacaine.

I am unable to understand and give consent for medical procedures.

I am not planning to join another clinical study while in this one.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an endoscopically guided injection of Exparel (Bupivacaine) or saline for the treatment of craniofacial pain

3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for changes in pain score and associated symptoms

3 weeks

Treatment Details

Interventions

• Exparel (Bupivacaine Liposome) (Local Anesthetic)

Trial Overview The study tests Exparel (Bupivacaine) injections against saline (placebo) in managing craniofacial pain. It's a double-blind study where neither doctors nor patients know who gets the real drug versus placebo, ensuring unbiased results.

Participant Groups

Group I: Exparel Active Control 1 Intervention

Patients receive an endoscopically guided injection of Exparel (Bupivacaine).

Group II: Saline Placebo Group 1 Intervention

Patients receive an endoscopically guided injection of saline

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

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]

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 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]

Exparel™ (DepoFoam bupivacaine) provides a longer-lasting nerve blockade (240 minutes) compared to standard bupivacaine solutions, which lasted 120 minutes and 210 minutes, indicating its potential for improved pain management.

While Exparel™ showed slightly higher inflammation scores than standard bupivacaine solutions shortly after injection, it had similar myotoxicity levels and no neurotoxicity, suggesting it may be a safe option for local anesthesia, though monitoring for tissue reactions is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multivesicular liposomal bupivacaine at the sciatic nerve. McAlvin, JB., Padera, RF., Shankarappa, SA., et al.[2022]

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]

Parotid duct injuries can lead to serious complications due to the complex anatomy of the buccal region, often requiring surgical intervention for proper management.

In a unique case, an epidural catheter was successfully used to treat a parotid duct injury, suggesting an alternative approach to traditional methods like microsurgical anastomosis or salivary flow diversion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parotid duct repair using an epidural catheter. Sujeeth, S., Dindawar, S.[2011]

Buccal fat pad (BFP) excision surgery is effective for reducing lower facial volume and improving facial contour, with significant changes observed in facial measurements 12 months post-surgery.

The study involved patients averaging 54 years old, and the surgery took about 60 minutes, demonstrating that BFP excision can lead to noticeable facial slimming and address sagging in middle-aged individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aesthetic Values of the Buccal Fat Pad Excision in Middle-Aged Patients. Kubo, T.[2022]

Botulinum toxin type A injections successfully treated a chronic salivary fistula in a 58-year-old woman after two unsuccessful surgeries, providing relief for 11 months without any adverse effects.

The treatment also significantly reduced facial synkinesis for 4 months, demonstrating the efficacy of botulinum toxin A in addressing both salivary discharge and facial muscle coordination issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of postparotidectomy salivary fistula with botulinum toxin. Guntinas-Lichius, O., Sittel, C.[2017]

The buccal fat pad (BFP) can effectively reconstruct various ventral skull base defects after expanded endonasal approaches (EEA), as demonstrated in a cadaveric study involving 10 BFPs from 5 specimens.

The study confirmed that the BFP has adequate vascular supply for use in endoscopic procedures, making it a viable option for flap reconstruction in select cases following EEA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The endonasal endoscopic harvest and anatomy of the buccal fat pad flap for closure of skull base defects. Markey, J., Benet, A., El-Sayed, IH.[2015]

In two case reports, botulinum toxin was successfully used to treat traumatic salivary gland fistulas, demonstrating its efficacy in promoting faster closure compared to spontaneous healing.

The use of botulinum toxin is highlighted as a minimally invasive and well-tolerated treatment option, suggesting it may be preferable to traditional surgical repair for managing salivary gland injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Botulinum toxin A as a treatment of traumatic salivary gland fistulas]. Breuer, T., Ferrazzini, A., Grossenbacher, R.[2018]

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

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. [2014]

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

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

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. Netherlands pubmed.ncbi.nlm.nih.gov

Multivesicular liposomal bupivacaine at the sciatic nerve. [2022]

7. 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]

8. Denmark pubmed.ncbi.nlm.nih.gov

Parotid duct repair using an epidural catheter. [2011]

9. England pubmed.ncbi.nlm.nih.gov

Aesthetic Values of the Buccal Fat Pad Excision in Middle-Aged Patients. [2022]

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

Treatment of postparotidectomy salivary fistula with botulinum toxin. [2017]

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

The endonasal endoscopic harvest and anatomy of the buccal fat pad flap for closure of skull base defects. [2015]

12. Germany pubmed.ncbi.nlm.nih.gov

[Botulinum toxin A as a treatment of traumatic salivary gland fistulas]. [2018]