Bupivacaine, Liposomal Bupivacaine, and Ropivacaine for Aortic Disease

(EXODUS Trial)

Overseen By Aseel Walker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Hartford Hospital

Must not be taking: Long-acting opioids

Disqualifiers: Emergency surgery, Allergy to anesthetics, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Intraoperative

14 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 undergoing certain types of vascular surgery, such as repairing an abdominal aortic aneurysm. Participants will receive either a single shot of a bupivacaine mixture (a local anesthetic) or continuous ropivacaine (another local anesthetic) through a catheter. The goal is to determine which method is safer and more effective for pain management and recovery. Ideal candidates are those scheduled for elective vascular surgery with a mid-abdominal incision and who are not currently experiencing severe symptoms. As a Phase 4 trial, this research involves treatments that are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

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.

What is the safety track record for these treatments?

Research has shown that liposomal bupivacaine is generally well-tolerated. One study found it reduced pain and the need for opioids after surgery. Some side effects were reported, but they are uncommon. Bupivacaine, another version of the drug, is also widely used and considered safe for pain management. However, some patients have experienced side effects like seizures, which can lead to breathing problems.

Ropivacaine, used in the standard care group, is known for its safety in managing pain. It has been used for a long time and is generally well-tolerated. Overall, these treatments are usually safe, but like any medical procedure, they can have risks. Always consult a healthcare provider before joining a trial to ensure it's right for you. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for aortic disease because they explore different formulations and applications of local anesthetics to potentially improve pain management during and after surgery. Unlike standard options, which typically use a single anesthetic like bupivacaine or ropivacaine, this trial investigates a combination of liposomal bupivacaine, bupivacaine, and ropivacaine, each with unique properties. Liposomal bupivacaine, in particular, is designed to release the anesthetic slowly, potentially providing longer-lasting pain relief. Additionally, the use of rectus sheath catheters for continuous infusion of ropivacaine allows for consistent pain management, which could enhance patient comfort and recovery.

What evidence suggests that this trial's treatments could be effective for aortic disease?

This trial will compare the effectiveness of different anesthetics for managing pain in aortic disease surgeries. Research has shown that liposomal bupivacaine, one of the treatments in this trial, does not consistently outperform regular bupivacaine in reducing post-surgery pain. Studies indicate it doesn't significantly enhance recovery or pain relief compared to standard bupivacaine, which effectively reduces post-surgery pain, especially when used in methods like epidurals. Another treatment option in this trial is ropivacaine, a common local anesthetic that effectively manages post-surgery pain. Studies support its ongoing use to reduce pain and the need for opioids. Both bupivacaine and ropivacaine have proven effective in managing pain in surgical settings. ^{2 3 4 6 7}

Who Is on the Research Team?

Kevin J Finkel, MD

Principal Investigator

Hartford Hospital

Are You a Good Fit for This Trial?

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.

Patients who are able to speak and read English

I was admitted to the hospital, found to need surgery while there, but have no symptoms of vascular problems.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Liposomal Bupivacaine
• Ropivacaine

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

Bupivacaine with a vasoconstrictor has a shorter onset time for local anesthesia compared to bupivacaine without a vasoconstrictor, but the duration of anesthesia is longer without the vasoconstrictor.

Using bupivacaine without a vasoconstrictor resulted in lower postoperative pain levels and better blood circulation, which is beneficial for the osseointegration of dental implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. Duka, M., Lazić, Z., Stamatović, N., et al.[2019]

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 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]

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]

A 45-year-old woman with severe digital ischemic pain showed marked improvement after receiving an axillary nerve block with liposomal bupivacaine (Exparel), suggesting its potential role in managing vasoocclusive symptoms despite being used off-label.

This case highlights the analgesic properties of liposomal bupivacaine in a patient who was not a candidate for surgical interventions, indicating that it may provide significant pain relief in similar cases of ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of digital ischemia with liposomal bupivacaine. Soberón, JR., Duncan, SF., Sternbergh, WC.[2021]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3659110/

Comparison of effects of epidural bupivacaine and ... In this prospective study, we aimed to compare the effects of epidural bupivacaine and intravenous meperidine on quality of recovery and postoperative outcomes ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01536717?term=ULTRACAIN&viewType=Table&rank=3

Comparison of the Local Anaesthetics Articaine and ... There is some evidence, that 0.5% bupivacaine reduces the acute post-sternotomy pain when infused constantly via catheters placed under the fascia (periosteal ...

3. nature.com nature.com/articles/aps201540

Differential effects of short- and long-term bupivacaine ... Results: Administration of bupivacaine (30–300 μmol/L) produced mild vasoconstriction, and this response declined with repeated administrations.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9743393/

Epidural bupivacaine-morphine analgesia versus patient- ... Conclusions: Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and ...

5. go.drugbank.com go.drugbank.com/drugs/DB00297

Bupivacaine: Uses, Interactions, Mechanism of Action Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7967071/

Effectiveness of Standard Local Anesthetic Bupivacaine and ... This randomized clinical trial investigates the effectiveness of liposomal bupivacaine vs standard bupivacaine for postoperative pain in patients with truncal ...

7. rapm.bmj.com rapm.bmj.com/content/48/Suppl_1/A44.2

EP011 Hemodynamic Effects of Spinal Anesthesia In ... Conclusions Spinal anesthesia in patients with AS did not result in refractory hypotension or adverse outcomes. These data suggest that AS should not constitute ...