Liposomal Bupivacaine vs. Bupivacaine for Wrist Fractures

(Vs Trial)

Overseen By Jay Schoenherr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Peripheral neuropathy, Neurological disorder, Pregnancy, 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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of pain relief for wrist surgeries: liposomal bupivacaine and plain bupivacaine. The researchers aim to determine which option better reduces post-surgery pain and whether they can help patients use fewer opioids. The trial includes individuals scheduled for wrist surgery who do not have nerve or brain conditions affecting the arm. Participants will receive either the experimental liposomal bupivacaine or the standard plain bupivacaine to compare outcomes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of potentially more effective pain management options.

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 this trial's treatments are likely to be safe?

Research has shown that liposomal bupivacaine (Exparel) is generally safe for people. In some studies, patients using Exparel required fewer painkillers in the first few days after surgery. However, many trials found that Exparel did not consistently provide better pain relief compared to other treatments.

Liposomal bupivacaine is approved for certain types of pain relief, indicating its safety for use. While it may not always be more effective at reducing pain, it remains generally safe for people.

Plain bupivacaine is also widely used and considered safe for pain relief, serving as the standard treatment for managing pain in these situations.

Both treatments have undergone thorough study, and any side effects are usually mild and temporary. Patients should always consult medical professionals to understand potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about liposomal bupivacaine for wrist fractures because it offers a potentially longer-lasting pain relief compared to standard bupivacaine. Liposomal bupivacaine uses a unique delivery system where the bupivacaine is encapsulated in tiny lipid spheres, allowing the drug to release slowly and extend its numbing effect. This could mean fewer doses and less frequent administration, which is a significant improvement over traditional bupivacaine treatments that typically require more frequent dosing.

What evidence suggests that this trial's treatments could be effective for wrist fractures?

This trial will compare liposomal bupivacaine with regular bupivacaine for wrist fractures. Research has shown that liposomal bupivacaine can help control pain after surgery. In one study, patients who received liposomal bupivacaine reported less pain on the day of surgery compared to those who received regular bupivacaine and required fewer pain medications. Another study found that liposomal bupivacaine provided good pain relief after wrist surgeries. These findings suggest it might manage pain better than regular bupivacaine for wrist fractures. ^{1 2 6 7 8}

Who Is on the Research Team?

Jay Schoenherr, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for individuals undergoing surgery to repair a distal radius fracture, commonly known as a broken wrist. Participants should be suitable for receiving nerve blocks for pain management post-surgery.

Inclusion Criteria

I am scheduled for wrist fracture repair at UNC Chapel Hill.

Exclusion Criteria

Pregnancy Pregnant women have physiologic changes that make them more sensitive to local anesthetics. That would introduce a confounding element in interpreting the effectiveness of the peripheral nerve blocks being studied.

I cannot have regional anesthesia due to health reasons.

I have severe nerve damage or a nerve disorder affecting my arms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Pre-operative

Participants receive a preoperative supraclavicular nerve block with either plain bupivacaine or liposomal bupivacaine

1 day

1 visit (in-person)

Post-operative

Participants are monitored for pain management and opioid consumption, with assessments up to 48 hours post-surgery

2 days

Follow-up via telephone

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine Hydrochloride
• Liposomal bupivacaine

Trial Overview

The study compares two types of medication used in supraclavicular nerve blocks: traditional Bupivacaine Hydrochloride and Liposomal bupivacaine (Exparel). The goal is to see which one provides better pain control after wrist fracture surgery.

How Is the Trial Designed?

Group I: Supraclavicular Liposomal Bupivacaine group Experimental Treatment 1 Intervention

This group will receive the liposomal bupivacaine

Group II: Supraclavicular Plain Bupivacaine group Active Control 1 Intervention

This group will receive the plain bupivacaine

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Published Research Related to This Trial

A single infusion of liposomal amphotericin B was found to be equally effective as the conventional treatment of amphotericin B deoxycholate, with similar cure rates of approximately 95% after 6 months in both treatment groups, involving a total of 412 patients.

Liposomal amphotericin B resulted in fewer severe adverse events compared to the conventional therapy, making it a safer and more cost-effective option for treating visceral leishmaniasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose liposomal amphotericin B for visceral leishmaniasis in India. Sundar, S., Chakravarty, J., Agarwal, D., et al.[2022]

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 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 of 20 patients undergoing lingual nerve microsurgery, those who received liposomal bupivacaine (LB) reported significantly less postoperative pain and consumed fewer opioid pills compared to those who received bupivacaine hydrochloride (BH).

The findings suggest that LB, with its prolonged duration of action, is more effective in reducing postoperative pain and opioid consumption, supporting its use in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine use in exploratory lingual nerve microsurgery: does liposomal bupivacaine use decrease postoperative pain and opioid consumption compared to bupivacaine hydrochloride? A pilot study. Jacobus, D., Mehr, S., Ziccardi, V.[2021]

In a study of 88,830 patients undergoing total knee arthroplasties, liposomal bupivacaine was used in 21.2% of cases but did not lead to a clinically meaningful reduction in inpatient opioid prescriptions or length of hospital stay.

The use of liposomal bupivacaine did not decrease the odds of opioid-related complications, suggesting it may have limited clinical impact in modern pain management settings that include peripheral nerve blocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Does Not Reduce Inpatient Opioid Prescription or Related Complications after Knee Arthroplasty: A Database Analysis. Pichler, L., Poeran, J., Zubizarreta, N., et al.[2019]

Liposomal amphotericin B demonstrated a faster recovery from fever and shorter hospital stays compared to pentavalent antimony salts in treating visceral leishmaniasis, based on a retrospective review of 17 patients.

Both treatments showed benefits, with pentavalent antimony salts improving biochemical and hematological parameters, indicating that each medication has its own advantages in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal amphotericin B versus pentavalent antimony salts for visceral Leishmania in children. Apa, H., Devrim, İ., Bayram, N., et al.[2013]

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 study involving 52 patients undergoing wrist surgeries, liposomal bupivacaine and standard bupivacaine HCl provided similar pain control and opioid usage in the first four postoperative days.

There were no significant differences in pain scores or opioid requirements between the two anesthetics, indicating that liposomal bupivacaine does not offer a clear advantage over bupivacaine HCl for early postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Extended-Release Liposomal Injection Versus Bupivacaine HCl for Early Postoperative Pain Control Following Wrist Operations: A Prospective, Randomized Control Trial. Dale, EL., Kluemper, CT., Cowart, SJ., et al.[2021]

In a study of 329 surgical patients, liposomal bupivacaine was initially associated with lower opioid use in the first 24 and 72 hours post-surgery compared to an elastomeric bupivacaine pump, suggesting it may provide effective pain relief.

However, after adjusting for confounding factors, there was no significant difference in opioid use between the two methods, indicating that both liposomal bupivacaine and the elastomeric pump are similarly effective for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine versus continuous infusion bupivacaine via an elastomeric pump for the treatment of postoperative pain. Kenes, MT., Leonard, MC., Bauer, SR., et al.[2019]

Lipid formulations of amphotericin B, such as liposomal amphotericin B, show reduced renal toxicity compared to traditional amphotericin B deoxycholate, but no formulation has demonstrated superior efficacy in well-designed studies.

A recent study found that while a standard dose of liposomal amphotericin B showed a numerically better response rate for treating invasive fungal infections compared to a higher loading dose, the increased nephrotoxicity in the loading dose group suggests it should not be used in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lipid formulations of amphotericin B in the management of invasive fungal infections]. Fohrer, C., Nivoix, Y., Moulin, JC., et al.[2019]

Liposomal amphotericin B (AmBisome) has been shown to be as effective as traditional amphotericin B deoxycholate in treating invasive fungal infections while significantly reducing toxic side effects like nephrotoxicity and infusion reactions.

Despite its higher acquisition costs, the cost-effectiveness of liposomal amphotericin B compared to amphotericin B deoxycholate and other antifungal agents remains unclear, highlighting the need for further pharmacoeconomic analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal amphotericin B: clinical experience and perspectives. Gibbs, WJ., Drew, RH., Perfect, JR.[2013]

Patients receiving bupivacaine liposome (Exparel) reported significantly lower pain levels and consumed fewer opioid pills on the day of surgery compared to those receiving standard bupivacaine (Marcaine).

However, the benefits of Exparel in reducing pain and opioid use were not sustained beyond the day of surgery, as no significant differences were observed in pain levels or total opioid consumption in the following days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Randomized Study Comparing Bupivacaine Hydrochloride Versus Bupivacaine Liposome for Pain Management After Distal Radius Fracture Repair Surgery. Alter, TH., Liss, FE., Ilyas, AM.[2018]

The new liposomal formulation of amphotericin B was found to be approximately three times more effective than conventional amphotericin B in treating visceral leishmaniasis in a murine model, with lower effective doses required for both strains of the parasite.

The liposomal formulation showed significantly higher drug accumulation in liver and spleen tissues without any observed toxicity, indicating a safer profile compared to the conventional formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of a new liposomal formulation of amphotericin B against two strains of Leishmania infantum in a murine model. Paul, M., Durand, R., Fessi, H., et al.[2020]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02515851

Study Details | NCT02515851 | Postsurgical Bupivacaine ...

THEORETICAL FRAMEWORK There is much research supporting that administration of liposomal bupivacaine is an effective post-surgical analgesic. The investigators' ...

2.

jhandsurg.org

jhandsurg.org/article/S0363-5023(19)31421-2/abstract

Bupivacaine Extended-Release Liposomal Injection ...

This study evaluated pain control after wrist operations using a long-acting local anesthetic, liposomal bupivacaine, compared with the ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37005638/

The use of liposomal bupivacaine in fracture surgery

This systematic review of the available data identified a total of eight studies evaluating the use of liposomal bupivacaine in patients with fractures.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10068181/

The use of liposomal bupivacaine in fracture surgery: a review

This systematic review of the available data identified a total of eight studies evaluating the use of liposomal bupivacaine in patients with fractures.

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0363502317300072

A Prospective Randomized Study Comparing Bupivacaine ...

Results. On the day of surgery, patients in the Exparel group reported significantly lower pain levels (3.9 vs 5.8) and consumed significantly fewer prescribed ...

6.

aetna.com

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

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ...

The mean amount of opioid rescue used over 72 hours was 76 mg for patients treated with Exparel and 103 mg for patients treated with placebo. The study was ...

7.

fda.gov

fda.gov/media/111001/download

EXPAREL

EXPAREL. ®. (bupivacaine liposome injectable suspension) is a long-acting, non-opioid analgesic. Bupivacaine, the active pharmaceutical ...

8.

journalofsurgicalresearch.com

journalofsurgicalresearch.com/article/S0022-4804(21)00124-4/abstract

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ...

Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs. Of the studies ...