Liposomal Bupivacaine vs Nerve Catheters for Post-Amputation Pain

Overseen By Janelle M Richard

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Aurora Quaye

Must not be taking: Opioids

Disqualifiers: Allergy to anesthetics, Coagulopathy, Substance use disorder, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two pain management methods for individuals who have had or will have a limb amputation. One method involves a nerve catheter, which places a tube near the nerves to continuously deliver pain medication. The other method uses a single injection of liposomal bupivacaine, a long-lasting pain reliever. The trial aims to determine which method better manages post-amputation pain. Individuals scheduled for a leg amputation or stump revision who can speak English might be suitable candidates for this trial. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on opioids over 90 MME/day, you cannot participate.

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 more than 90 morphine milligram equivalents of opioids per day, you cannot participate.

What is the safety track record for these treatments?

Research has shown that liposomal bupivacaine is generally safe for patients. Studies have found that common side effects, such as nausea, fever, and constipation, affect more than 10% of people. This treatment acts as a local anesthetic, blocking nerve signals to stop pain.

The FDA has already approved liposomal bupivacaine for pain relief after surgery, confirming its well-established safety. While side effects can occur, serious problems remain rare.

Additionally, mixing liposomal bupivacaine with regular bupivacaine hydrochloride has proven successful in various surgeries, even in young patients. This supports its safety when used as part of a nerve block, which is under consideration in this trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for post-amputation pain, like continuous nerve catheters, rely on a steady infusion of anesthetics to manage discomfort. However, liposomal bupivacaine stands out because it uses a special delivery system that slowly releases the drug over time. This means potentially longer-lasting pain relief from a single injection, reducing the need for continuous infusions and possibly minimizing side effects. Researchers are excited about this because it could simplify post-surgical care and improve patient comfort significantly.

What evidence suggests that this trial's treatments could be effective for post-amputation pain?

This trial will compare liposomal bupivacaine with a continuous perineural popliteal nerve block catheter for post-amputation pain. Studies have shown that liposomal bupivacaine reduces pain after surgery by slowly releasing pain relief over time, maintaining lower pain levels for up to 72 hours. As a result, patients often require fewer opioid painkillers. Research also indicates that it can shorten hospital stays and lower pain scores compared to traditional pain relief methods. This treatment has effectively managed pain from various surgeries, making it a promising option for relieving pain after amputation. ^{6 7 8 9 10}

Who Is on the Research Team?

Aurora Quaye, MD

Principal Investigator

MaineHealth

Are You a Good Fit for This Trial?

This trial is for individuals scheduled for primary below-knee amputation or stump revision, who can understand and consent in English. They should not have a severe allergy to local anesthetics, infections where the needle will go, extreme obesity (BMI > 40), bleeding disorders, be on high-dose opioids (>90 MME/day), have substance use disorders, or need emergency amputations.

Inclusion Criteria

English speaking

You have a certain level of physical health, as classified by the American Society of Anesthesiologists.

You are planning to have a surgery to remove a limb or revise the remaining part of a limb.

Exclusion Criteria

You have been diagnosed with a substance use disorder.

Patients unable to cooperate or consent to the study

You are allergic to local anesthetics.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a continuous perineural popliteal nerve block catheter or a single shot perineural popliteal nerve block for pain management post-below knee amputation

72 hours

Follow-up

Participants are monitored for opioid consumption, length of stay, and phantom limb pain

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine Hydrochloride 0.5 % Injectable Solution
• Liposomal bupivacaine

Trial Overview

The study compares two pain management methods after leg amputations: Liposomal bupivacaine versus continuous nerve catheters with Bupivacaine Hydrochloride. It's designed to gather initial data at Maine Medical Center to plan a larger future study.

How Is the Trial Designed?

Group I: Continuous perineural popliteal nerve block catheter Active Control 1 Intervention

Placement of continuous perineural popliteal nerve block catheter with injection of 30cc 0.5% bupivacaine within one hour prior to surgery, followed by continuous infusion of 10cc 0.3% ropivacaine (current standard practice) for at least 72 hours following surgery. Saphenous single shot 20cc 0.2

Group II: Single Shot Perineural Popliteal Nerve Block Active Control 1 Intervention

Single shot perineural popliteal nerve block injection of 10cc 13.3% liposomal bupivacaine combined with 15cc 0.50% bupivacaine hydrochloride within one hour prior to surgery

Liposomal bupivacaine is already approved in United States, European Union for the following indications:

Approved in United States as Exparel for:

• Postsurgical pain in adults

Approved in European Union as Exparel liposomal for:

• Local pain relief around small to medium-sized surgical wounds
• Regional pain relief in the surgery of the knee and around the shoulders

Who Is Running the Clinical Trial?

Aurora Quaye

Lead Sponsor

Trials

1

Recruited

10+

Ryan Mountjoy, MD

Lead Sponsor

Trials

1

Recruited

30+

MaineHealth

Collaborator

Trials

76

Recruited

43,800+

Published Research Related to This Trial

In a study of 631 patients undergoing major lower-extremity amputation, peripheral nerve blockade significantly reduced opioid use in the first 72 hours post-surgery compared to those who received only general anesthesia.

The addition of liposomal bupivacaine to standard bupivacaine in nerve blocks did not result in a significant difference in opioid consumption compared to using standard bupivacaine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral Nerve Blockade with Combined Standard and Liposomal Bupivacaine in Major Lower-Extremity Amputation. Dumitrascu, CI., Warner, NS., Stewart, TM., et al.[2022]

In a study of 40 patients undergoing forefoot surgery, those who received liposomal bupivacaine consumed significantly fewer narcotic pills on the first two postoperative days compared to the control group, indicating its effectiveness in reducing opioid consumption.

Patients receiving liposomal bupivacaine reported lower pain scores during the first four days after surgery, and there were no increased wound complications, suggesting it is a safe and effective addition to postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine in forefoot surgery. Robbins, J., Green, CL., Parekh, SG.[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 of 90 patients undergoing immediate breast reconstruction, the use of liposomal bupivacaine (LB) significantly reduced postoperative pain scores compared to traditional pain management methods, indicating its efficacy as a pain reliever.

Patients receiving LB also had a shorter hospital stay (1.5 days) compared to those on narcotics (2.0 days), with no reported adverse events, highlighting its safety and potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. Butz, DR., Shenaq, DS., Rundell, VL., 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 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]

In a study of 69 patients who underwent below knee amputations, those who received liposomal bupivacaine (LB) nerve blocks consumed significantly less opioids post-surgery, averaging 25.0 oral morphine equivalents (OME) compared to 50.5 OME in the control group.

The use of LB nerve blocks not only reduced opioid consumption but also resulted in a higher percentage of patients using minimal opioids, suggesting that LB may be an effective alternative for pain management after amputation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Liposomal Bupivacaine in Regional Nerve Blocks for Below Knee Amputations. Allsbrook, AP., Gotsch, A., To, J., et al.[2023]

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 randomized controlled trial involving 57 patients undergoing midurethral sling placement, liposomal bupivacaine resulted in lower median pain scores on postoperative day 1 compared to a mixture of bupivacaine and lidocaine (20 mm vs 30 mm), indicating some efficacy in pain management.

Despite the initial lower pain scores, there were no significant differences in overall opioid and nonsteroidal anti-inflammatory drug consumption or in quality of recovery scores after 7 days, suggesting that liposomal bupivacaine may not provide a clinically significant advantage over traditional pain management methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. Iwanoff, C., Salamon, C.[2020]

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EXPAREL

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NCT07212114 | Efficacy of EXPAREL vs. Bupivacaine

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This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks. Methods: Data ...