Bupivacaine, Liposomal Bupivacaine, and Ropivacaine for Aortic Disease

(EXODUS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Kevin J Finkel, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Hartford Hospital

Must not be taking: Long-acting opioids

Disqualifiers: Emergency surgery, Allergy to anesthetics, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this randomized clinical trial is to compare single shot rectus sheath blocks of liposomal bupivacaine/bupivacaine mixture to bilateral rectus sheath catheters infused with ropivacaine (standard of care at our facility) in patients undergoing vascular surgery with an open mid-abdominal laparotomy incision. This study will examine the difference in the highest, lowest, average, and current pain scores reported at the end of 24-48 postoperative hours using the brief pain inventory-short form (BPI-SF). Participants will be randomized to either receive a single dose of liposomal bupivacaine/bupivacaine mixture intraoperatively at the end of surgery through bilateral rectus sheath blocks (LB/B group) or to receive the standard of care ropivacaine intraoperatively at the end of surgery through bilateral rectus sheath blocks with the insertion of bilateral RS catheter for continuous ropivacaine infusion plus repeated daily boluses (Catheter group; standard care). They will be assessed for a difference in postoperative pain scores, opioid consumption, hospital and PACU length of stay, patient's satisfaction, and quality of recovery. Additionally, we will examine the resources consumed by each intervention, including the medication cost (ropivacaine vs. LB/bupivacaine mixture), block and catheter supply, hospital length of stay, and anesthesia billing time.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on long-acting opioids or use more than 50 MME of opioids daily, you may not be eligible to participate.

Is the combination of Bupivacaine, Liposomal Bupivacaine, and Ropivacaine safe for humans?

Bupivacaine and its liposomal form (EXPAREL) have been shown to be safe in various medical procedures, such as breast augmentation and obstetrical analgesia, with minimal side effects when used correctly. However, there have been reports of serious complications like respiratory distress when bupivacaine is injected incorrectly, such as into the wrong area near the eye. ^{1 2 3 4 5}

How does the drug for aortic disease differ from other treatments?

This treatment uses liposomal bupivacaine, which is a long-acting form of bupivacaine designed to release the drug slowly over time, potentially providing extended pain relief compared to standard formulations. While liposomal bupivacaine is typically used for postoperative pain management, its use in aortic disease may offer unique benefits due to its prolonged analgesic effects. ^{2 6 7 8 9}

Research Team

Kevin J Finkel, MD

Principal Investigator

Hartford Hospital

Eligibility Criteria

This trial is for adults aged 18-80 undergoing elective vascular surgery with an open mid-abdominal incision. Candidates must speak/read English, have an ASA score I-IV, and not be on high-dose opioids or have chronic pain syndrome. Exclusions include emergency surgeries, allergies to local anesthetics, substance abuse within 3 months, and certain medical conditions.

Inclusion Criteria

I am scheduled for surgery on the main blood vessels in my abdomen.

I am between 18 and 80 years old.

Patients who are able to speak and read English

Exclusion Criteria

My cancer has spread to distant parts like bone, lung, or brain.

You have had an allergic reaction to numbing medicine used for surgeries or procedures.

I cannot have RSB due to certain health issues like past surgeries or infections.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a single dose of liposomal bupivacaine/bupivacaine mixture or standard care ropivacaine through bilateral rectus sheath blocks and catheters during surgery

Intraoperative

Postoperative Monitoring

Participants are monitored for pain scores, opioid consumption, and other outcomes for up to 168 postoperative hours

1 week

Daily assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of patient satisfaction and quality of recovery

2 weeks after discharge

Treatment Details

Interventions

• Bupivacaine (Local Anesthetic)
• Liposomal Bupivacaine (Local Anesthetic)
• Ropivacaine (Local Anesthetic)

Trial Overview The study compares liposomal bupivacaine/bupivacaine mixture in single shot rectus sheath blocks versus standard care ropivacaine in catheters for post-surgery pain management. It measures pain scores, opioid use, hospital stay duration, patient satisfaction and recovery quality over a period of up to two days after surgery.

Participant Groups

Group I: RSB LB/B Experimental Treatment 2 Interventions

Rectus Sheath Block: Total 60mL: (20mL 1.3% LB + 30mL 0.25% bupivacaine + 10mL NS) (30mL per side)

Group II: RSB/RSC Ropivacaine Active Control 1 Intervention

Rectus Sheath Block: Total 60mL of 0.2% ropivacaine (3 vials) (30mL per side) + Rectus Sheath Catheter intermittent hourly boluses of 0.2% ropivacaine 10mL/hr per side

Who Is Running the Clinical Trial?

Hartford Hospital

Lead Sponsor

Trials

140

Recruited

19,700+

Dr. Ajay Kumar

Hartford Hospital

Chief Medical Officer since 2016

MD, University of Connecticut School of Medicine

Jeffrey A. Flaks

Hartford Hospital

Chief Executive Officer since 2019

Master's in Health Administration, George Washington University

Findings from Research

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

Retrobulbar bupivacaine (0.75%) can lead to serious complications such as respiratory distress and central nervous system disturbances, as shown in three reported cases.

These complications may arise from accidental injection into blood vessels or the sheath surrounding the optic nerve, highlighting the need for careful administration techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory depression following retrobulbar bupivacaine: three case reports and literature review. Rodman, DJ., Notaro, S., Peer, GL.[2013]

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]

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]

References

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

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

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]

3. France pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. [2013]

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

Respiratory depression following retrobulbar bupivacaine: three case reports and literature review. [2013]

5. Serbia pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. [2019]

6. 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]

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

Treatment of digital ischemia with liposomal bupivacaine. [2021]

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

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

9. England pubmed.ncbi.nlm.nih.gov

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