Liposomal Bupivacaine for Peripheral Arterial Disease

Overseen By Joshua Druckrey

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Opioids

Disqualifiers: Chronic pain, Allergy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a special pain relief injection, liposomal bupivacaine, can reduce the need for strong pain medications during and after surgery to improve blood flow in the legs. The trial includes two groups: one receives the liposomal bupivacaine injection, while the other receives a placebo (a harmless, inactive substance). Individuals planning leg circulation surgery, who do not have chronic pain or current opioid use, might be suitable candidates. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on opioids for more than one week, you cannot participate.

What is the safety track record for these treatments?

Studies have shown that liposomal bupivacaine is generally safe for use. Common side effects include fever, dizziness, and swelling, occurring in about 2% to 10% of users.

Research has also found that side effects related to the nervous system and heart are similar to those seen with regular bupivacaine and a placebo. This suggests that liposomal bupivacaine is not more dangerous than these other options.

The FDA has already approved this treatment for other uses, which helps confirm its safety. However, like any medication, it can have side effects, so discussing its suitability with a healthcare provider is important. ^{1 2 3 4}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about liposomal bupivacaine for peripheral arterial disease because it offers a novel approach to pain management following revascularization surgery. Most standard treatments focus on general pain relief using opioids or non-steroidal anti-inflammatory drugs (NSAIDs), which can have significant side effects. However, liposomal bupivacaine provides targeted, local pain control directly at the surgical site, potentially reducing the need for systemic pain medications. Its unique liposomal formulation allows for a slow, sustained release of the anesthetic, which could enhance comfort and improve recovery time for patients. This treatment approach could transform post-surgical pain management by minimizing reliance on more traditional medications.

What evidence suggests that liposomal bupivacaine might be an effective treatment for reducing narcotic use in peripheral arterial disease?

This trial will compare liposomal bupivacaine, also known as EXPAREL, with a placebo for pain relief during lower extremity revascularization surgery. Research has shown that the FDA has approved liposomal bupivacaine for certain uses, and it is being studied for its potential to reduce the need for opioid painkillers after surgery. Studies indicate that it can help reduce opioid use, benefiting patients who want to avoid these drugs. In animal studies, it provided longer-lasting pain relief than some traditional methods. However, other studies suggest that regular bupivacaine might work better for pain control in some situations. Overall, liposomal bupivacaine has shown promise in reducing pain and narcotic use, but results can vary depending on its application. ^{2 4 5 6 7}

Who Is on the Research Team?

Tiziano Tallarita, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals scheduled for elective lower extremity revascularization surgery who are not on opioids for more than a week, do not have chronic pain, and have no allergies to local anesthetics or contraindications to regional anesthesia.

Inclusion Criteria

You are scheduled for a planned surgery to improve blood flow in your legs.

Exclusion Criteria

Non-English speaking

Long-lasting pain

You have been taking opioid medications for more than 1 week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo lower extremity revascularization surgery with either liposomal bupivacaine or placebo injection

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for narcotic use and pain management in the first 72 hours post-surgery

3 days

Daily assessments (in-person or via call)

Follow-up

Participants are monitored for recovery quality and narcotic use at 14 and 28 days post-surgery

28 days

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine liposome
• Placebo

Trial Overview The study is testing if injections of liposomal bupivacaine can reduce the need for narcotic drugs during and after leg artery surgery. Participants will either receive the actual drug or a placebo without knowing which one they get.

How Is the Trial Designed?

Group I: Liposomal Bupivacaine Group Experimental Treatment 1 Intervention

Subjects will receive an injection of liposomal bupivacaine during clinically indicated lower extremity revascularization surgery.

Group II: Placebo Group Placebo Group 1 Intervention

Subjects will receive an injection of placebo during clinically indicated lower extremity revascularization surgery.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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 823 patients across various surgical settings, liposome bupivacaine demonstrated a lower incidence of adverse events (62%) compared to bupivacaine HCl (75%) and placebo (43%), indicating better tolerability.

Serious adverse events were less common in the liposome bupivacaine group (2.7%) compared to bupivacaine HCl (5.4%), suggesting that liposome bupivacaine may be a safer option for local analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of liposome bupivacaine, a novel local analgesic formulation. Viscusi, ER., Sinatra, R., Onel, E., et al.[2022]

A 45-year-old woman with severe digital ischemic pain showed marked improvement after receiving an axillary nerve block with liposomal bupivacaine (Exparel), suggesting its potential role in managing vasoocclusive symptoms despite being used off-label.

This case highlights the analgesic properties of liposomal bupivacaine in a patient who was not a candidate for surgical interventions, indicating that it may provide significant pain relief in similar cases of ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of digital ischemia with liposomal bupivacaine. Soberón, JR., Duncan, SF., Sternbergh, WC.[2021]

A review of 76 randomized controlled trials found that only 11% showed a significant benefit of liposomal bupivacaine over standard bupivacaine or ropivacaine for postoperative pain control.

The majority of trials indicated that unencapsulated bupivacaine provided better pain relief than liposomal bupivacaine, suggesting that routine use of liposomal bupivacaine may not be justified based on current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Ilfeld, BM., Eisenach, JC., Gabriel, RA.[2021]

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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf

EXPAREL (bupivacaine liposome injectable suspension) The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered ...

2. withpower.com withpower.com/trial/phase-4-lower-extremity-revascularization-8-2023-ea31f

Liposomal Bupivacaine for Peripheral Arterial Disease In a pilot study involving 25 pigs, subarachnoid administration of liposomal bupivacaine resulted in a longer duration of pain relief compared to standard ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33372949/

Clinical Effectiveness of Liposomal Bupivacaine ... Ninety-two percent of trials (11 of 12) suggested a peripheral nerve block with unencapsulated bupivacaine provides superior analgesia to infiltrated liposomal ...

4. aetna.com aetna.com/cpb/medical/data/900_999/0941.html

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ... ... injectable liposomal bupivacaine suspension (EXP). Main outcome measures included cumulative opioid use, daily mean patient-reported pain scores, and ORAEs ...

5. mdpi.com mdpi.com/2077-0383/13/24/7586

Admixture of Liposomal Bupivacaine and ... Liposomal bupivacaine is currently approved by the United States Food and Drug Administration (FDA), with limited indications, including interscalene, popliteal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11975001/

Real-World Pharmacovigilance Analysis of Adverse Events ... The analysis revealed 8,023 AE reports in total. Liposomal bupivacaine had 58 positive safety signals, 24 of which were off-label and listed in ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26204387/

Safety and Side Effect Profile of Liposome Bupivacaine ... Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs ...