Epidural vs Local Anesthesia for Post-Surgical Pain Relief

Recruiting at 1 trial location

Overseen By Rebecca L Stone, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Coagulation disorder, Infection, Spinal pathology, 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: Unknown

Duration: 0 to 48 hours postoperatively

106 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to test the hypothesis that surgical site infiltration with liposomal bupivacaine (LB) is non-inferior to and more cost effective than thoracic epidural analgesia (TEA) for patients undergoing open gynecologic surgery on an established enhanced recovery program (ERP) using a non-inferiority randomized trial design. The impact of TEA and surgical site infiltration with LB on neuroendocrine and inflammatory mediators of surgical stress response (SSR) will also be investigated as a translational endpoint.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a history of long-term opioid use, you may not be eligible to participate.

What data supports the effectiveness of the drug Liposomal Bupivacaine (Exparel) for post-surgical pain relief?

Liposomal Bupivacaine (Exparel) has been shown to effectively reduce postoperative pain and the need for opioids in various surgeries, such as total knee arthroplasty and pharyngoplasty, by providing long-lasting pain relief. ^{1 2 3 4 5}

Is liposomal bupivacaine (Exparel) generally safe for use in humans?

Liposomal bupivacaine (Exparel) has been shown to be safe in various clinical settings, including breast augmentation and pediatric pharyngoplasty, and is approved for use in surgical site pain relief. However, it is not approved for use in the neuraxial space (around the spinal cord), and some studies have examined its safety in off-label uses, such as peripheral nerve blocks. ^{1 3 4 5 6}

How does liposomal bupivacaine differ from other drugs for post-surgical pain relief?

Liposomal bupivacaine (Exparel) is unique because it is a long-acting local anesthetic that provides extended pain relief by slowly releasing the drug over time, unlike traditional bupivacaine which acts more quickly but for a shorter duration. It is administered directly into the surgical site, offering targeted pain control, and is an alternative to thoracic epidural analgesia, which is more invasive. ^{1 3 4 5 7}

Research Team

Rebecca L Stone, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

This trial is for adults over 18 who are scheduled for open gynecologic surgery. It's not suitable for those with conditions that make epidural analgesia risky, bleeding disorders, infections at the potential epidural site, certain brain pathologies, a history of long-term opioid use, spinal abnormalities, contraindications to liposomal bupivacaine or severe liver disease.

Inclusion Criteria

I am scheduled for abdominal surgery by a cancer specialist at the trial's hospital.

Exclusion Criteria

I do not have brain conditions causing increased pressure or blocking fluid flow.

My liver disease is classified as moderate to severe.

I have a blood clotting disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either thoracic epidural analgesia or surgical site infiltration with liposomal bupivacaine during and after open gynecologic surgery

0 to 48 hours postoperatively

Follow-up

Participants are monitored for safety, effectiveness, and recovery outcomes, including pain management and return of bowel function

Up to 30 days post discharge

Long-term Follow-up

Participants are assessed for long-term outcomes such as hospital readmission rates and overall recovery

Up to 1 year

Treatment Details

Interventions

• Liposomal bupivacaine
• Thoracic epidural analgesia (bupivacaine)

Trial Overview The study compares two pain relief methods after open gynecologic surgery: thoracic epidural analgesia (TEA) using bupivacaine and surgical site infiltration with liposomal bupivacaine (LB). The aim is to see if LB is as effective and more cost-efficient than TEA without compromising recovery.

Participant Groups

Group I: Arm 2: Surgical Site Infiltration with Liposomal Bupivacaine Experimental Treatment 1 Intervention

Liposomal bupivacaine (LB) surgical site infiltration: A single 20 mL liposomal bupivacaine vial containing 266 mg of free-base bupivacaine will be mixed with 60 mL of 0.25% bupivacaine hydrochloride (HCl) and then diluted in preservative-free sterile 0.9% saline for maximal volume not to exceed 300 mL. Dilution with 0.9% saline will be dependent upon length of surgical incision per protocol. The solution will be injected using 22-gauge needle in equal distribution into the peritoneum, along the fascia and into the subcutaneous tissues of the surgical wound by trained faculty surgeons.

Group II: Arm 1: Thoracic Epidural Analgesia with bupivicaine Experimental Treatment 1 Intervention

Thoracic epidural analgesia (TEA): 0.125 % Bupivicaine infusion (5-7 milliliter \[mL\] per hour) intraoperatively with a 3 mL bolus at the end of the operative procedure just prior to emergence from general anesthesia. Postoperatively 0.0625% Bupivicaine until patient-controlled epidural analgesia (PCEA) pump. PCEA pump 0.0625% bupivacaine at 5-7 mL per hour infusion with a 3 mL q20 minutes demand. PCEA discontinuation with oral tolerance.

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Pacira Pharmaceuticals, Inc

Industry Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

Findings from Research

Liposomal bupivacaine (LB) is safe for use in pediatric patients and significantly improves pain control after pharyngoplasty, as evidenced by lower pain scores compared to those receiving standard lidocaine.

Patients treated with LB had earlier oral intake, required fewer opioids, and were discharged from the hospital nearly 2 days earlier than those in the control group, highlighting its efficacy in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. Day, KM., Nair, NM., Griner, D., et al.[2018]

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]

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 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 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]

Liposomal bupivacaine (LB) provided significantly lower pain scores and reduced postoperative opioid use compared to traditional thoracic epidural bupivacaine hydrochloride (TE BH) in a study of 190 matched patients undergoing video-assisted thoracoscopic pulmonary resection (VATS-R).

LB also resulted in lower hospital costs and a higher percentage of patients being discharged directly home, indicating it may be a more effective and cost-efficient alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cost and outcomes in patients receiving thoracic epidural versus liposomal bupivacaine for video-assisted thoracoscopic pulmonary resection. Medina, M., Foiles, SR., Francois, M., et al.[2019]

References

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

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. [2018]

2. 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]

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

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

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

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

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

Comparison of cost and outcomes in patients receiving thoracic epidural versus liposomal bupivacaine for video-assisted thoracoscopic pulmonary resection. [2019]