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Comparative Effectiveness Between Indomethacin and Pancreatic Stenting in the Prevention of Post ERCP Pancreatitis

Primary Purpose

Post ERCP Pancreatitis

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
pancreatic stenting
Indomethacin
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Post ERCP Pancreatitis focused on measuring post ERCP panceatitis, rectal indomethacin, pancreatic stents

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

presence of one of the following risk factors for Post ERCP Pancreatitis

  1. sphincter of Oddi dysfunction
  2. history of PEP, pancreatic instrumentation or sphincterotomy, precut sphincterotomy,
  3. difficult cannulation defined by >5 cannulation attempts
  4. the use of double wire technique in bile duct access
  5. at least 2 of the followings including i) female age<50 ii) 3 pancreatograms iii) acinarization (contrast injection to tail fo pancreas). iv) normal bilirubin; v)guidewire to the tail of pancreas or secondary branches.

Exclusion Criteria:

  • patients intended for pancreatic stenting e.g. those with pancreatic duct strictures, ampullectomy,
  • without informed consents from patient or next of kin
  • age <18
  • pregnant or lactating women
  • patients with altered anatomy except except Billroth I and II gastrectomy
  • contraindications to the use of NSAIDs such as those with active gastrointestinal bleeding, renal failure (serum creatinine > 140)
  • known NSAID allergy
  • incipient heart failure.

Sites / Locations

  • Endoscopy centreRecruiting
  • Eastern Hepatobiliary Surgery Hospital,Endoscopy centreRecruiting
  • Endoscopy centre
  • Endoscopy centreRecruiting
  • Endoscopy centreRecruiting
  • Endoscopy Centre, Prince of Wales HospitalRecruiting
  • 2. Chulalongkorn University and King Chulalongkorn Memorial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

indomethacin

pancreatic stenting

indomethacin plus pancreatic stenting

Arm Description

rectal indomethacin 100 mg to be administered before or after ERCP

a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire)

[rectal indomethacin 100 mg to be administered before or after ERCP] plus [a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire]

Outcomes

Primary Outcome Measures

post-ERCP pancreatitis
Percentage of Participants with post ERCP pancreatitis
high severity of post-ERCP pancreatitis
Percentage of Participants with high severity of post-ERCP pancreatitis using the Clavian-Dindo classification (1 / 2 / 3 / 3a / 3b / 4 / 4a/ 4b / 5)
pancreatitis with complications
Percentage of Participants with pancreatitis with complications using Atlanta classification (Mild / Moderate / Severe / Critical )

Secondary Outcome Measures

hospital stay
period of hospitalisation (days)
endoscopic intervention due to PEP
Percentage of Participants with endoscopic intervention due to Post ERCP pancreatitis
radiologic intervention due to PEP
Percentage of Participants with radiologic intervention due to Post ERCP pancreatitis
surgery due to PEP
Percentage of Participants with Surgical intervention due to Post ERCP pancreatitis

Full Information

First Posted
August 23, 2018
Last Updated
October 12, 2022
Sponsor
Chinese University of Hong Kong
Collaborators
Xijing Hospital, Changhai Hospital, Tianjin Union Medical Center, Zhejiang University, Eastern Hepatobiliary Surgery Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03713879
Brief Title
Comparative Effectiveness Between Indomethacin and Pancreatic Stenting in the Prevention of Post ERCP Pancreatitis
Official Title
Comparative Effectiveness Between Rectally Administered Indomethacin and Pancreatic Stenting in the Prevention of Post Endoscopic Retrograde Cholangio-panceaticography (ERCP) Pancreatitis: a Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2019 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong
Collaborators
Xijing Hospital, Changhai Hospital, Tianjin Union Medical Center, Zhejiang University, Eastern Hepatobiliary Surgery Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Post ERCP pancreatitis (PEP) occurs in 4 to 5% of patients and is associated with significant morbidities and occasional mortalities. The use of rectall administered indomethacin and pancreatic duct stent (PDS) placement have independently been proven to reduce PEP. The comparative effectiveness of the two methods has however not been studied. It is argued that in the context of indomethacin, the placement of a PDS is unnecessary. Advocates for PDS insertion however believe that mechanical decompression of the pancreatic duct is critical in the prevention of pancreatitis. The investigators propose a multi-centre randomised controlled trial to compare the use of rectal indomethacin to PDS insertion in high risk patients in the prevention of PEP.
Detailed Description
Background of research Pancreatitis is the most common complication after Endoscopic retrograde cholangiopancreatography (ERCP). It occurs in approximately 5% of patients. The risk can approach 20 to 30% in those with known pre- and intra-procedural risk factors. Three in 100 patients with post ERCP pancreatitis (PEP) consequently die. The placement of pancreatic duct stent and the use of rectal administered indomethacin have both been independently shown to reduce PEP. The placement of a pancreatic duct stent has been for a long time considered the gold standard in the prophylaxis against PEP. In a meta-analysis of 8 RCTs that compared the use of pancreatic duct stents to no treatment, pancreatic duct stenting in high risk patients reduces incidence of PEP by approximately 5 fold. In a landmark study by Elmunzer et al., rectal administered indomethacin was shown to reduce PEP (52 of 307 patients,16.9% to 27 of 295 patients, 9.2%, P=0.005). In the trial, >80% received pancreatic duct stents in addition to rectal indomethacin. Overall there have been 7 RCTs on the use of rectal indomethacin all showing benefits with its use, 3 with PDS and 4 without. In the literature, there has been no direct comparison between the use of rectal indomethacin alone and insertion of PDS. In a secondary analysis of the trial by Elmunzer et al., PEP following the use of rectal indomethacin alone was less compared with the placement of PDS. In a meta-analysis by Akbar et al. pooling 29 studies (22 PDS and 7 indomethacin), the use of rectal indomethacin alone was associated with fewer PEP when compared to insertion of PDS on an indirect comparison using network metaanalysis (OR 0.48, 95%CI 0.26-0.87). The more favorable results with rectal indomethacin alone raised the question if PDS insertion is necessary. Furthermore, in another secondary analysis, patients after failed PDS insertion had a 34.7% rate of pancreatitis. In contrary, the rate of pancreatitis was 16.4% in those after successful PDS and 12.1% after no attempt at PDS insertion. The SVI (stent versus indomethacin) trial (NCT024762279) by the US cooperative for Outcomes Research in Endoscopy (USCORE) group is an ongoing non-inferiority trial that compares indomethacin alone to the combination of indomethacin and PDS in 1430 high risk patients with the primary outcome of pancreatitis. The trial tests the hypothesis that PDS is no longer necessary in the context of rectal indomethacin. The rationale for the trial has been based on the secondary analysis of the Elmunzer trial and the network analysis aforementioned. The investigators argue that the relative merits of rectal indomethacin and PDS placement have not been established. There may have been substantial difference in the baseline risks between the trials using either rectal indomethacin and PDS placement alone. The small number of RCTs over the use of rectal indomethacin may have overestimated its beneficial effect especially among patients at lower risk of PEP. A direct comparison in the form of a RCT to compare effectiveness of both treatment modalities is required. The insertion of PDS may continue to be important in patients contraindicated for the use of NSAIDs. Research plan and methodology The investigators hypothesize that rectal administration of indomethacin is not inferior to placement of a pancreatic duct stent in the prevention of pancreatitis after ERCP in high risk patients. In patients randomised to receive pancreatic duct stents, the investigators sought to determine the success rate with PDS insertion and outcomes following successful or unsuccessful PDS insertion. In addition, the investigators analyse possible factors to PEP in both cohorts of patients on either indomethacin or PDS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post ERCP Pancreatitis
Keywords
post ERCP panceatitis, rectal indomethacin, pancreatic stents

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
rectal indomethacin 100 mg to be administered before or after ERCP a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire) or a PD stent plus rectal indomethacin 100 mg before or after ERCP In patients randomized to receive PD stenting, the number of attemtps is limited to 5.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1734 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
indomethacin
Arm Type
Experimental
Arm Description
rectal indomethacin 100 mg to be administered before or after ERCP
Arm Title
pancreatic stenting
Arm Type
Experimental
Arm Description
a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire)
Arm Title
indomethacin plus pancreatic stenting
Arm Type
Experimental
Arm Description
[rectal indomethacin 100 mg to be administered before or after ERCP] plus [a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire]
Intervention Type
Device
Intervention Name(s)
pancreatic stenting
Intervention Description
a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire)
Intervention Type
Drug
Intervention Name(s)
Indomethacin
Other Intervention Name(s)
indocid
Intervention Description
rectally administered indomethacin before or after ERCP
Primary Outcome Measure Information:
Title
post-ERCP pancreatitis
Description
Percentage of Participants with post ERCP pancreatitis
Time Frame
30 days
Title
high severity of post-ERCP pancreatitis
Description
Percentage of Participants with high severity of post-ERCP pancreatitis using the Clavian-Dindo classification (1 / 2 / 3 / 3a / 3b / 4 / 4a/ 4b / 5)
Time Frame
30 days
Title
pancreatitis with complications
Description
Percentage of Participants with pancreatitis with complications using Atlanta classification (Mild / Moderate / Severe / Critical )
Time Frame
30 days
Secondary Outcome Measure Information:
Title
hospital stay
Description
period of hospitalisation (days)
Time Frame
30 days
Title
endoscopic intervention due to PEP
Description
Percentage of Participants with endoscopic intervention due to Post ERCP pancreatitis
Time Frame
30 days
Title
radiologic intervention due to PEP
Description
Percentage of Participants with radiologic intervention due to Post ERCP pancreatitis
Time Frame
30 days
Title
surgery due to PEP
Description
Percentage of Participants with Surgical intervention due to Post ERCP pancreatitis
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: presence of one of the following risk factors for Post ERCP Pancreatitis sphincter of Oddi dysfunction history of PEP, pancreatic instrumentation or sphincterotomy, precut sphincterotomy, difficult cannulation defined by >5 cannulation attempts the use of double wire technique in bile duct access at least 2 of the followings including i) female age<50 ii) 3 pancreatograms iii) acinarization (contrast injection to tail fo pancreas). iv) normal bilirubin; v)guidewire to the tail of pancreas or secondary branches. Exclusion Criteria: patients intended for pancreatic stenting e.g. those with pancreatic duct strictures, ampullectomy, without informed consents from patient or next of kin age <18 pregnant or lactating women patients with altered anatomy except except Billroth I and II gastrectomy contraindications to the use of NSAIDs such as those with active gastrointestinal bleeding, renal failure (serum creatinine > 140) known NSAID allergy incipient heart failure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James LAU, MD
Phone
35051411
Email
laujyw@surgery.cuhk.edu.hk
First Name & Middle Initial & Last Name or Official Title & Degree
RAYMOND TANG, MD
Phone
35052640
Email
raymondtang@cuhk.edu.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James LAU, MD
Organizational Affiliation
Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Endoscopy centre
City
Xi'an
State/Province
Shan XI
ZIP/Postal Code
710000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Lin Pan, MD
Email
panyl@fmmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Pang Yang Lin, MD
First Name & Middle Initial & Last Name & Degree
Kai Chun Wu, MD
Facility Name
Eastern Hepatobiliary Surgery Hospital,Endoscopy centre
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bing HU, MD
Email
drhubing@aliyun.com
First Name & Middle Initial & Last Name & Degree
Bing Hu, MD
Facility Name
Endoscopy centre
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Bai, MD
Email
baiyu1998@hotmail.com
First Name & Middle Initial & Last Name & Degree
YU Bai, MD
Facility Name
Endoscopy centre
City
Tianjin
State/Province
Tian Jin
ZIP/Postal Code
300000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen Li, MD
Email
drliwen@126.com
First Name & Middle Initial & Last Name & Degree
Wen Li, MD
Facility Name
Endoscopy centre
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yun Sheng Qing, MD
Email
175260446@qq.com
First Name & Middle Initial & Last Name & Degree
Yun sheng Qing, MD
Facility Name
Endoscopy Centre, Prince of Wales Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Y LAU, Prof
Phone
+85235051411
Email
laujyw@surgery.cuhk.edu.hk
Facility Name
2. Chulalongkorn University and King Chulalongkorn Memorial Hospital
City
Bangkok
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Supakarn Chaithongrat, MD
Email
pangicu@hotmail.com
First Name & Middle Initial & Last Name & Degree
Parit Mekaroonkamol, MD
Email
parit_m@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
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Comparative Effectiveness Between Indomethacin and Pancreatic Stenting in the Prevention of Post ERCP Pancreatitis

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