Epidural vs Local Anesthesia for Post-Surgical Pain Relief

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Rebecca L Stone, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Coagulation disorder, Infection, Spinal pathology, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

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 2 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 2 4 5 7}

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 18 years old or older.

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.

Trial 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 (Local Anesthetic)
• Thoracic epidural analgesia (bupivacaine) (Local Anesthetic)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Johns Hopkins Baltimore, MD

Johns Hopkins Hospital Baltimore, MD

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Lead Sponsor

Pacira Pharmaceuticals, Inc Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022] Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks.

2. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019] An injectable liposomal bupivacaine suspension (EXPAREL™) is approved by the US Food and Drug Administration for analgesia by tissue infiltration and interscalene brachial plexus, but not for use in the neuraxial space. This pilot study describes neurological and histological outcomes of escalating doses of this extended-release formulation of bupivacaine after subarachnoid administration.

3. 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] Liposomal bupivacaine (Exparel) is a long-acting local anesthetic preparation with demonstrated efficacy over placebo in reducing postoperative pain and opioid requirement. Limited comparative efficacy and cost-effectiveness data exist for its use in total knee arthroplasty (TKA) when used in a multimodal, opioid-sparing analgesic and anesthetic approach. We hypothesized that liposomal bupivacaine offers no clinical advantage over our standard of care but carries significant economic impact.

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

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Pharyngoplasty. [2018] Liposomal bupivacaine (LB, Exparel) is a long-acting local anesthetic reported to decrease postoperative. The authors demonstrate the first safe use of LB in pediatric patients with improved pain control following pharyngoplasty.

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

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020] Liposomal bupivacaine (Exparel®) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve toxicity and clinical effectiveness of perineural Exparel® alone or with added dexamethasone in a mouse model.

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] The long-acting preparation of bupivacaine, liposomal bupivacaine (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), was approved by the Food and Drug Administration in October 2011 and has been shown to be safe in breast augmentation. It remains to be established if liposomal bupivacaine provides superior pain control in this setting.

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] Thoracic Epidural has long been the most recommended treatment for postoperative pain management in general thoracic surgery. This study compares liposomal bupivacaine (LB) as an alternative method for pain control and compares it to the standard.