| CTRI Number |
CTRI/2025/09/094129 [Registered on: 02/09/2025] Trial Registered Prospectively |
| Last Modified On: |
02/09/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Surgical/Anesthesia |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A Study Comparing Two Endoscopic Ultrasound-Guided Nerve Block Methods to Relieve Pain in People with Advanced Pancreatic or Bile Duct Cancer |
|
Scientific Title of Study
|
Endoscopic ultrasound guided central versus bilateral celiac plexus neurolysis for pain management in advanced pancreatobiliary cancer: An Assessor blinded randomised controlled trial |
| Trial Acronym |
nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Manish Panwar |
| Designation |
Senior Resident |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Gastromedicine
Dehradun UTTARANCHAL 249203 India |
| Phone |
9654758445 |
| Fax |
|
| Email |
manishpanwar392@gmail.com |
|
Details of Contact Person Scientific Query
|
| Name |
Dr Itish Patnaik |
| Designation |
Associate Professor |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Gastromedicine
Dehradun UTTARANCHAL 249203 India |
| Phone |
8825564938 |
| Fax |
|
| Email |
patnaik.itish@gmail.com |
|
Details of Contact Person Public Query
|
| Name |
Manish Panwar |
| Designation |
Senior Resident |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Gastromedicine
New Delhi DELHI 110019 India |
| Phone |
9654758445 |
| Fax |
|
| Email |
manishpanwar392@gmail.com |
|
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Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
AIIMS Rishikesh |
| Address |
Virbhadra Road, Rishikesh
Uttarakhand- 249 203, India |
| Type of Sponsor |
Government medical college |
|
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Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Manish Panwar |
AIIMS Rishikesh |
Department of Gastromedicine Dehradun UTTARANCHAL |
9654758445
manishpanwar392@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| AIIMS Rishikesh Institutional Ethics Comittee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C258||Malignant neoplasm of overlappingsites of pancreas, (2) ICD-10 Condition: C240||Malignant neoplasm of extrahepaticbile duct, (3) ICD-10 Condition: C23||Malignant neoplasm of gallbladder, (4) ICD-10 Condition: C229||Malignant neoplasm of liver, not specified as primary or secondary, (5) ICD-10 Condition: C228||Malignant neoplasm of liver, primary, unspecified as to type, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
BILATERAL CELIAC PLEXUS NEUROLYSIS |
Bilateral approach After initially identifying the celiac axis and superior mesenteric artery take off, the preloaded needle will be advanced to the base of the celiac artery. echoendoscope will then be torqued clockwise until the celiac artery and superior mesenteric artery could no longer been seen. The needle will be then advanced alongside the celiac artery and superior mesenteric artery as far as the region lateral to the base of the superior mesenteric artery takeoff. Bupivacaine (10 cc) then will be injected while withdrawing the needle to distribute the anesthetic from the region of the superior mesenteric artery takeoff up to the base of the celiac takeoff. The needle will then be advanced and repositioned next to the base of the superior mesenteric artery. The empty bupivacaine syringe will be removed and replaced with a 10cc syringe of absolute alcohol. The alcohol then will be distributed from the region lateral to the base of the superior mesenteric artery up to the base of the celiac axis. Then the echoendoscope will be torqued counterclockwise until the celiac axis and superior mesenteric artery could not be seen and the needle will be advanced to the right lateral base of the superior mesenteric artery. A second 10 cc syringe of absolute alcohol will be injected from the region of the base of the superior mesenteric artery to the base of the celiac axis and then withdrawn. To ensure that the needle tip is not in a vessel, suction will be applied before injecting in all cases. |
| Comparator Agent |
CENTRAL CELIAC PLEXUS NEUROLYSIS |
In the central approach,an 22 gauge needle will be used for puncture. It will be advanced to a point just above the origin of the celiac artery while confirming vascular landmarks with the colour Doppler. After confirming the lack of backflow of blood with aspiration, 10 mL of 0.5 percent bupivacaine will be injected to prevent neurolytic agent induced pain. Upon confirming that the patient stable condition and no blood on repeat aspiration, 20 ml of absolute ethanol will be injected. Moderate resistance should be observed while injecting alcohol and any lack of such resistance might suggest that the vascular space has been punctured. In this case, the syringe plunger should be withdrawn to apply negative pressure to assess the return of the blood inside the syringe. In case of blood in the syringe needle depth will be adjusted to avoid intravascular injection. While injecting snowstorm appearance due to hyper-echoic alcohol solution will be noted at the injection site. Post injection needle will be flushed with 3ml of saline to remove residual alcohol within the needle and the needle will be withdrawn. In case of hypotension, the patient will receive additional fluid resuscitation with normal saline. |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1.Age (more than 18 years)
2.Diagnosis or suspected to have unresectable pancreaticobiliary malignancy on cross-sectional imaging which is already proven or subsequently found to have confirmed malignancy on pathology either by cytology or histopathology.
3.Any level of abdominal or back pain considered to be potentially related to the mass with a score of more than or equal to 4 on an 11-point VAS with the use of Opioids to control pain.
Characteristics of the pain as follows:
a.New onset (less than 3 months)
b.Constant
c.Centrally located
d.No obvious other source of pain
4.No possibility of immediate surgical management. Based on EUS/Cross sectional imaging based on arterial and venous involvement or evidence of distant metastases. Involvement of more than 50% of the circumference of the superior mesenteric vein, portal vein, or spleno-portal confluence/any involvement of superior mesenteric artery, celiac axis, or hepatic artery; or (cytologically proven nonregional lymphadenopathy
5.Patients willing to participate in the study
6.Celiac axis accessible for both unilateral and bilateral neurolysis at EUS
|
|
| ExclusionCriteria |
| Details |
1.Abnormal clotting (international normalized ratio more than equal to 1.5) or reduced platelet count (less than equal to 50000per micorLitre) which cannot be corrected.
2.Presence of gastric and or esophageal varices precluding the path of CPN.
3.History of prior CPN
4.Use of anticoagulation or antiplatelet agent which cannot be stopped
5.Patients with performance status ECOG 4
6. Prior upper abdominal surgery or an anatomic abnormality making endoscopic access impossible or localization of celiac plexus difficult
7.History of allergy to bupivacaine or alcohol
8.Severe cardiorespiratory illness causing procedure unsafe for the patient.
9.Patients with evidence of dementia or altered mental status that would prohibit the giving and understanding of informed consent, and no evidence of psychiatric risk that would preclude adequate compliance with this protocol.
10.Patient with evidence of significant active infection (pneumonia, peritonitis, wound sepsis)
11.Patient with evidence of serious ongoing illness such as uncontrolled metabolic disease (diabetes mellitus, hypothyroidism)
12.Moderate to gross ascites
|
|
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Method of Generating Random Sequence
|
Permuted block randomization, variable |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare the pain response rate on Visual analog scale score among both the groups on day 7 post Endoscopic ultrasound-guided celiac plexus neurolysis. |
DAY 7 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To compare the pain response rate on Visual analog scale score among both the groups on day 30 post Endoscopic ultrasound-guided celiac plexus neurolysis. |
DAY 30 |
| To compare the percentage pain score reduction from baseline on Visual analog scale score on day 7 and day 30. |
DAY 7 AND 30 |
| To compare the complete pain response rates at day 7 and day 30 |
DAY 7 AND 30 |
| To compare the pain non-response rate at day 7 and day 30 |
DAY 7 AND 30 |
| To compare the intake of an opioid analgesic in terms of morphine equivalent in milligram at day 7 and day 30 compared to baseline |
DAY 7 AND 30 |
| To compare the Incidence of adverse effects if any |
|
| The SF-36 Version-2 will be also used to assess Qulaity of living. Questionnaire responses were collected before the intervention and on day 7 and 30 after intervention. |
DAY 7 AND 30 |
| To compare 90 days survival rate between the two groups |
day 90 |
| To compare Duration of pain relief: Patients with positive responses were continuously monitored every monthly to determine the duration of treatment efficacy. When the pain score reaches baseline or more. Follow-up will be terminated as this reflected a loss of pain relief. Patients will be followed by on day 7,30,60 and 90. |
day 7, 30.60 and 90. |
|
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Target Sample Size
|
Total Sample Size="140" Sample Size from India="140"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
30/09/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0" Months="0" Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Patients with Pancreatico-biliary malignancies have disabling abdominal pain which is a frequent symptom in patients due to the perineural invasion of tumor cells, and present in 70%–90% of the patients at diagnosis and has very complex medical management. It markedly reduces the quality of life and is considered a prognostic factor for survival. Medical management for pain is often challenging and usually begins with the administration of nonopioid analgesics followed by opioids in refractory cases. High dosage of analgesics often cause reduction in patient’s survival & hamper Quality of Living. Opioids often provide suboptimal pain relief but have many adverse effects, such as nausea, constipation, urinary retention, drowsiness, and can lead to patient tolerance. The Celiac plexus (CP) is responsible for transmitting pain sensations originating from the upper abdominal organs, including the pancreas, liver, gallbladder, stomach, and ascending and transverse colons. When a neurolytic agent is injected into the celiac plexus, it disrupts the transmission of pain signals from afferent nerves to the spinal cord. Traditionally, access to the celiac plexus has been done under fluoroscopic, computed tomography (CT) guided, ultrasound (USG) guided. These guided procedures were technically difficult and it was necessary to avoid the different structures while performing access to celiac plexus.However, endosonographic (EUS) approach is advantageous in multiple ways. Firstly, it allows CPN to be performed close enough to the celiac plexus through the gastric wall, which is much safer and has more effective access. Secondly, Better control of the needle above or lateral to the celiac trunk, real-time guidance, short puncture distance, use of the anterior pathway, avoiding puncture through the posterior diaphragm space and use of Doppler to visualize vessel interposition. Endosonography-guided celiac plexus neurolysis (EUS-CPN) was first introduced by Faigel et al. and Wiersema in 1996. It is an alternative in patients who have refractory pain or cannot tolerate increasing amounts of opioid medications or analgesic ceiling is achieved because of neurotoxicity. EUS-CPN is performed to ameliorate pain and reduce the dosage of analgesics. Furthermore, a recent study suggested that early EUS-CPN provides better pain-relief and greater reduction in morphine consumption than conventional management. EUS-CPN achieve chemical ablation of the nerve tissue by injection of Absolute ethanol (usual neurolytic agent) and local anaesthetic (mainly bupivacaine) into the celiac plexus. It induces a local inflammatory reaction which is followed by fibrosis during the healing process. The timing of the celiac intervention relative to pain onset appears to be an important predictor of pain response in patients with pancreatic cancer. Early pancreatic cancer pain appears to derive mainly from the celiac plexus involvement, while pain during the terminal stages of the disease may also involve other visceral, bone metastasis and somatic nerves involvement. Thus, CPN performed soon after the onset of pain from pancreatic cancer may increase the rate of response. EUS-CPN is performed by 2 Approaches. Firstly, is the central technique which involves injection of a neurolytic agent at the base of the celiac axis. In the bilateral technique, the neurolytic agent is injected on both sides of the celiac axis. This study aims to assess and compare the pain response rate & efficacy in patients undergoing EUS-CPN for refractory pain via both techniques i.e. Unilateral and Bilateral approach. |