Pain Control Methods for Pancreatic Cancer Surgery

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Chronic opioids

Disqualifiers: Coagulopathy, Local anesthetic allergy, 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: Up to 96 hours

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two methods for managing pain after pancreatic cancer surgery. One method involves a rectus sheath block, where a long-acting anesthetic called liposomal bupivacaine is injected into the abdominal muscle layers. The other method uses thoracic epidural analgesia (TEA), which places a tiny tube near the spine to deliver pain medication. Researchers aim to determine which method better controls pain without causing side effects like low blood pressure. Candidates for this trial include individuals undergoing pancreatic cancer surgery who do not regularly use opioids. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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 using chronic opioids, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that thoracic epidural analgesia (TEA) might provide slightly better pain relief than other methods, such as intravenous morphine, in the days following surgery. Studies indicate that TEA can lead to fewer complications and improved pain control during this period. However, it may sometimes cause low blood pressure, which patients should be aware of.

Alternatively, using liposomal bupivacaine in a rectus sheath block has also proven effective. Although data on this method is limited, some studies suggest it does not lead to higher opioid use or worse pain compared to other forms of bupivacaine, a long-lasting pain reliever.

Both methods have been used safely in surgeries. The choice between them often depends on the specific needs and conditions of the patient. Discussing these options with a healthcare provider is important to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these pain control methods for pancreatic cancer surgery because they offer innovative approaches to managing postoperative discomfort. Unlike standard treatments that often rely on systemic opioids, the Rectus Sheath Block with Liposomal Bupivacaine delivers pain relief directly to the abdominal area, potentially reducing the need for opioids and their side effects. On the other hand, Thoracic Epidural Analgesia provides continuous pain relief through a targeted delivery system, which can offer superior pain management compared to traditional methods. Both techniques aim to improve patient recovery by minimizing pain and enhancing comfort after surgery.

What evidence suggests that this trial's pain control methods could be effective for pancreatic cancer surgery?

This trial will compare two pain control methods for pancreatic cancer surgery. Research has shown that thoracic epidural analgesia (TEA), administered to participants in one arm of this trial, can relieve pain slightly better than intravenous morphine in the first few days after surgery. However, TEA might cause low blood pressure, which can limit its use. Another arm of this trial will study the rectus sheath block with liposomal bupivacaine. Studies have found that this method can be as effective as TEA for managing pain after pancreatic surgery. Liposomal bupivacaine is a long-lasting pain reliever that works when injected into the muscle layers of the abdomen. Both treatments aim to control pain effectively, with the rectus sheath block possibly having fewer side effects. ^{1 2 3 4 6}

Who Is on the Research Team?

James Flaherty

Principal Investigator

University of Minnesota Masonic Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients undergoing pancreatoduodenectomy, a surgery for pancreatic and duodenal tumors. Participants must be eligible for the surgical procedure and fit enough to receive either of the pain control methods being tested.

Inclusion Criteria

I am 18 or older and will have a specific pancreatic surgery at the University of Minnesota.

Exclusion Criteria

Patients unable to understand the quality of recovery survey due to intellectual barriers (to be determined by the primary investigator/attending anesthesiologist's discretion)

Patient refusal and those who have opted out of research

Pregnant patients (will be assessed through review of the medical record)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Patients undergo either thoracic epidural analgesia or rectus sheath block with liposomal bupivacaine prior to pancreatoduodenectomy

Up to 96 hours

In-hospital stay

Follow-up

Participants are monitored for opioid consumption, pain scores, and return of bowel function

Up to 7 days

In-hospital monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Rectus Sheath Block with Liposomal Bupivacaine
• Thoracic Epidural Analgesia

Trial Overview The study compares rectus sheath block with liposomal bupivacaine—a long-acting local anesthetic—against thoracic epidural analgesia (TEA), which delivers pain medication directly near the spine. The goal is to determine which method offers better post-surgery pain relief without causing low blood pressure.

How Is the Trial Designed?

Group I: Group RS (rectus sheath block) Experimental Treatment 5 Interventions

Prior to pancreatoduodenectomy, patients undergo ultrasound and receive bupivacaine and liposomal bupivacaine injection into the rectus sheath.

Group II: Group E (TEA) Experimental Treatment 7 Interventions

Prior to pancreatoduodenectomy, patients undergo thoracic epidural placement and receive bupivacaine and hydromorphone continuous infusion via epidural for up to 72 hours postoperatively. Patients also receive iopamidol via epidural and undergo x-ray imaging on study.

Rectus Sheath Block with 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
• Local pain relief by injecting it around the edges of small to medium-sized surgical wounds

Approved in European Union as Exparel liposomal for:

• Local pain relief by injecting it around the edges of small to medium-sized surgical wounds
• Regional pain relief by injecting it around the nerves that supply the lower limbs or the shoulder

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Transversus abdominis plane (TAP) blocks with liposomal bupivacaine provided pain relief at rest that was non-inferior to epidural analgesia in patients recovering from major abdominal surgery, with a minimal difference in pain scores.

However, patients receiving TAP blocks required more opioids than those with epidurals, but experienced significantly less hypotension, suggesting TAP blocks may be safer for patients at risk of low blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial. Turan, A., Cohen, B., Elsharkawy, H., 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]

In a study of 84 patients who underwent pancreaticoduodenectomy, the use of rectus sheath catheters (RSCs) significantly reduced postoperative opiate consumption compared to standard care, with a median reduction of 54.4 mg of oral morphine equivalents at 96 hours post-surgery.

Despite the reduced opiate use, there was no significant difference in pain scores between the RSC group and the control group, indicating that RSCs can effectively lower opiate needs without compromising pain management or increasing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study. Tapley, PLC., Van der Vyver, M., Coburn, NG., et al.[2023]

In a study of 24 patients with metastatic pancreatic cancer, both neurolytic celiac plexus block (NCPB) and epidural 5% butamben suspension (EBS) provided significant pain relief, with EBS showing a higher overall success rate (85% vs. 55%).

Both interventions were found to be safe, with no serious complications reported, and they similarly reduced opioid use, indicating that EBS is a viable alternative to NCPB for managing pain in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of epidural butamben to celiac plexus neurolytic block for the treatment of the pain of pancreatic cancer. Shulman, M., Harris, JE., Lubenow, TR., 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]

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]

Celiac plexus block (CPB) significantly reduces pain in pancreatic cancer patients, with a mean difference in pain scores of -0.42 at four weeks and -0.44 at eight weeks compared to control, indicating its efficacy as a pain management technique.

CPB also leads to lower opioid consumption, suggesting it may be a safer alternative with fewer adverse effects than traditional opioid therapies, although further research is needed to confirm its effectiveness compared to other analgesic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiac plexus block for pancreatic cancer pain in adults. Arcidiacono, PG., Calori, G., Carrara, S., et al.[2022]

In a study of 100 patients undergoing elective laparoscopic colectomy, those receiving liposomal bupivacaine TAP blocks required significantly less narcotic medication (5.06 mg) compared to those receiving standard bupivacaine (18.75 mg), indicating better pain management.

Patients treated with liposomal bupivacaine also experienced earlier bowel function (1.7 days vs 2.4 days) and shorter hospital stays (2.7 days vs 3.4 days), suggesting improved postoperative recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Surgery: Better Pain Control and Patient Outcomes with Liposomal Bupivacaine than Bupivacaine. Guerra, L., Philip, S., Lax, EA., et al.[2020]

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 90 patients undergoing immediate breast reconstruction, the use of liposomal bupivacaine (LB) significantly reduced postoperative pain scores compared to traditional pain management methods, indicating its efficacy as a pain reliever.

Patients receiving LB also had a shorter hospital stay (1.5 days) compared to those on narcotics (2.0 days), with no reported adverse events, highlighting its safety and potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. Butz, DR., Shenaq, DS., Rundell, VL., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06411795

Rectus Sheath Block With Liposomal Bupivacaine Versus ... This phase II trial compares the effect of rectus sheath block with liposomal bupivacaine to thoracic epidural analgesia (TEA) on pain control in patients ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2024-02287

Rectus Sheath Block with Liposomal Bupivacaine versus ... Rectus sheath blocks with liposomal bupivacaine may be as effective as TEA in reducing pain in patients following a pancreatoduodenectomy. Eligibility ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10918720/

Liposomal bupivacaine for ultrasound‐guided rectus ... Spread patterns and effectiveness for surgery after ultrasound‐guided rectus sheath block in adult day‐case patients scheduled for umbilical ...

4. clinconnect.io clinconnect.io/trials/NCT06411795

Rectus Sheath Block With Liposomal Bupivacaine Versus This phase II trial compares the effect of rectus sheath block with liposomal bupivacaine to thoracic epidural analgesia (TEA) on pain control in patients ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002961024002782

Postoperative pain scores and opioid use after standard ... FPBs with standard bupivacaine were not associated with higher 72-h opioid use or more severe pain compared to liposomal bupivacaine.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05224089

Bilateral TAP and RS Blocks Using Liposomal Bupivacaine ... This study will be a single center, prospective triple blinded randomized controlled study, comparing the use of liposomal bupivacaine (Exparel) to regular ...