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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to find out if using liposomal bupivacaine solution (bupivacaine liposome) injections during lower extremity revascularization surgery will lower the amount of narcotic drugs used during and following the procedure.

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 data supports the effectiveness of the drug liposomal bupivacaine for treating peripheral arterial disease?

A case report showed that liposomal bupivacaine (Exparel) helped improve symptoms in a patient with digital ischemia, a condition related to poor blood flow, suggesting it might help with similar blood flow issues. However, broader studies on its use for pain control after surgery found mixed results, with many trials not showing significant benefits over standard treatments. ^{1 2 3 4 5}

Is liposomal bupivacaine safe for use in humans?

Liposomal bupivacaine (Exparel) has been studied for safety in various uses, including surgical site pain relief and peripheral nerve blocks. It is generally considered safe when used as approved, but off-label uses may carry risks, such as delayed nerve inflammation, as seen in some animal studies. ^{1 3 4 5 6}

How does the drug liposomal bupivacaine differ from other treatments for peripheral arterial disease?

Liposomal bupivacaine is unique because it is a sustained-release formulation that can be used in peripheral nerve blocks to provide longer-lasting pain relief, which may help manage symptoms of peripheral arterial disease. Unlike standard treatments, it is not typically used for this condition, but its vasodilating and analgesic properties have shown potential in managing ischemic symptoms. ^{1 2 3 4 5}

Research Team

Tiziano Tallarita, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

References

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

Treatment of digital ischemia with liposomal bupivacaine. [2021]

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

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

The safety of liposome bupivacaine, a novel local analgesic formulation. [2022]