EUS-CPN With and Without Bupivacaine

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04951804
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Centre hospitalier de l'Université de Montréal (CHUM)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

ANAND V SAHAI, MD
Principal Investigator Affiliation Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Canada
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pancreatic Cancer
Additional Details

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.

Arms & Interventions

Arms

Active Comparator: EUS-CPN with bupivacaine

Endoscopic ultrasound guided celiac plexus neurolysis with absolute alcohol 20 mL preceded by injection of 10 ml of bupivacaine 0.5%.

Experimental: EUS-CPN without bupivacaine

Endoscopic ultrasound guided celiac plexus neurolysis with absolute alcohol 20 mL only.

Interventions

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.

Procedure: - 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.

Contact a Trial Team

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International Sites

Montreal, Quebec, Canada

Status

Recruiting

Address

Centre de recherche du Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 0A9

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