EUS-CPN With and Without Bupivacaine

Pancreatic Cancer Clinical Trial

— EUS-NB  

Official title:

A Randomized Controlled Trial of Endoscopic Ultrasound Guided Celiac Plexus Neurolysis (EUS-CPN) With and Without Bupivacaine

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04951804
• Other study ID #: 21.151
• Status: Recruiting
• Phase: N/A
• Start date: October 7, 2021
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: CHARLES MACKAY, RN
• Phone: 514-890-8000
• Email: charles.mackay.chum[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endoscopic ultrasound (EUS) allows EUS-guided trans gastric injection of absolute alcohol around the base of the celiac plexus (celiac plexus neurolysis (EUS-CPN)), to help alleviate pain associated with pancreatic cancer.

It is standard procedure to inject bupivacaine immediately before injecting absolute alcohol, to theoretically prevent pain that may occur during and after the procedure. However, there are no data showing whether bupivacaine injection has any real influence on intra-procedural, immediate post-procedural, or long-term pain control. The injection of bupivacaine before the alcohol may have no effect, a synergistic effect, or an antagonistic effect, by diluting the alcohol, and reducing its neurolytic capacity. Inadvertent intravascular injection of bupivacaine may also cause irreversible cardiac arrhythmias and death.

The investigators therefore propose a randomized clinical trial to determine whether the exclusion of bupivacaine during EUS-guided CPN improves outcomes, or not.

Description:

Pancreatic malignancies are the second most frequent gastrointestinal malignancy in Canada. From cancer mortality statistics in 2014, there were 4,700 new cases of pancreatic malignancies second only to colorectal cancer, representing 2.4% of all cancers. Even with chemotherapy, the median survival for patients with pancreatic adenocarcinoma is 6 to 10 months. Few patients are diagnosed at a resectable stage (12%-20%) so many patients are candidates for palliation only.

In this context, one of the most important symptoms is pain because it often affects both quality of life and survival. 70 to 80 % of patients with pancreatic cancer have abdominal pain at the time of diagnosis. Adequate pain control is therefore an essential component of care in these patients. In the initial phase, the pain is visceral, but with disease progression, somatic pain may occur, especially due to the peri-pancreatic invasion of neural structures, such as the celiac plexus.

Standard analgesics such as acetaminophen are usually ineffective and the use and effectiveness of opioids is frequently limited by side effects such as nausea, constipation, somnolence, confusion or respiratory depression.

The celiac plexus is immediately adjacent to the gastric wall. Endoscopic ultrasound (EUS) allows EUS-guided trans gastric injection of neurolytic agents around the celiac plexus (celiac plexus neurolysis [CPN]). Under conscious sedation, the echoendoscope is advanced into the stomach, just distal to the gastro-esophageal junction. The region of the celiac plexus is identified around the takeoff of the celiac artery from the aorta. Then, under real-time ultrasound guidance, a 19g needle is used to inject a neurolytic agent such as absolute alcohol around the base of the celiac artery. The entire procedure takes approximately 5 minutes. Absolute alcohol causes the immediate destruction of the celiac plexus neurons, by precipitation of endoneural lipoproteins and mucoproteins.

The effectiveness of CPN, is well established. It is safe, produces significant pain reduction, significantly reduces narcotic requirements, and may even increase survival. The investigators were the first to publish a randomized, sham-controlled trial demonstrating the efficacy of EUS-CPN for pain due to pancreatic cancer, and authored the most recent published guidelines on the use of EUS-CPN.

Based on our experience in over 1000 neurolysis procedures, patients undergoing EUS-guided CPN may experience pain, acutely during alcohol injection, and sometimes post-procedure, for up to a few hours. (Unpublished observations) It is possible that the presence of pain during injection of alcohol indicates that the celiac plexus has been accurately targeted and may therefore portend better long-term pain control.

Currently, during the neurolysis procedure, it is standard procedure to inject bupivacaine immediately before injecting absolute alcohol, to theoretically prevent pain during and after the procedure.

The true value of bupivacaine during neurolysis has never been studied. There are no data showing whether bupivacaine injection has any real influence on intra-procedural, immediate post-procedural, or long-term pain control. The injection of bupivacaine before the alcohol may have no effect, a synergistic effect, or an antagonistic effect, by diluting the alcohol, and reducing its neurolytic capacity. Inadvertent intravascular injection of bupivacaine may also cause irreversible cardiac arrhythmias and death.

In other words, in the worst case scenario, the injection of bupivacaine may increase procedural risk, without any associated benefit in terms of pain reduction.

The EUS team at the CHUM stopped using bupivacaine during neurolysis approximately 2 years ago and has noticed no obvious difference in pain during the procedure or in the immediate post-procedure recovery period, no increase in complications, and a possible reduction in requests for repeat neurolysis - suggesting that neurolysis without bupivacaine may be more effective. (Unpublished observations)

The investigators therefore propose a randomized clinical trial to determine whether the exclusion of bupivacaine during EUS-guided CPN improves outcomes, or not.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Malignant-appearing pancreatic mass, or proven pancreatic cancer involving the pancreatic genu, body, or tail

2. Any level of abdominal or back pain considered to be potentially related to the mass:

1. New onset pain (<3 months)

2. Constant

3. Centrally located

4. With or without irradiation to the back

5. No obvious other source of pain based on history and physical examination by the attending endosonographer

3. No possibility of surgical management

4. Signed, informed consent

5. Celiac axis accessible for bilateral neurolysis at EUS.

Exclusion Criteria:

1. Allergy to bupivacaine

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• EUS-CPN without bupivacaine
Under conscious sedation, an echoendoscope is advanced into the stomach, just distal to the gastro-esophageal junction. The region of the celiac plexus is identified around the takeoff of the celiac artery from the aorta. Then, under real-time ultrasound guidance, a 19g needle is used to inject a neurolytic agent such as absolute alcohol around the base of the celiac artery.
• EUS-CPN with bupivacaine
Under conscious sedation, an echoendoscope is advanced into the stomach, just distal to the gastro-esophageal junction. The region of the celiac plexus is identified around the takeoff of the celiac artery from the aorta. Then, under real-time ultrasound guidance, a 19g needle is used to firstly inject bupivacaine and secondly a neurolytic agent such as absolute alcohol around the base of the celiac artery.

Locations

Country	Name	City	State
Canada	Centre de recherche du Centre hospitalier de l'Université de Montréal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Likert pain scores	Pain scale used : 7-point Likert scale for pain (minimum value is 0, maximum value is 6; higher scores mean a worse outcome)	Day 0 and Day 30
Secondary	Difference in pain scores at T0 vs all other follow-up time points	The 7-point Likert scale for pain (minimum value is 0, maximum value is 6; higher scores mean a worse outcome)	Days 0, 3, 7, 30, 60, 90, 120
Secondary	Time to discharge from the endoscopy unit	Time spent in the recovery room following the procedure	From time of arrival in the recovery room after the intervention to time of discharge from the recovery room. The estimated period of time over which the event is assessed is up to two hours
Secondary	Narcotic usage	Change in cumulative narcotic usage between Day 0 and Day 60, and between Day 0 and Day 120	Narcotic usage for the 3 day-period preceding Days 0, 60 and 120
Secondary	Adverse events	Rate of all intervention-specific adverse events (Using the American Society of Gastrointestinal Endoscopy classification)	Days 0, 3, 7, 30, 60, 90, 120
Secondary	Survival	Number of days between the EUS-CPN intervention and death	Up to 18 months
Secondary	Difference in Global Rating Scale of Change at T3 vs all other follow-up time points	The Global Rating Scale of Change will be used to measure subjects' impression of improvement in their health condition after T0 (the day celiac plexus neurolysis is performed) (minimum value is 0, maximum value is 6; higher scores mean a better outcome)	Days 3, 7, 30, 60, 90, 120