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

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ClinicalTrials.gov Identifier: NCT03713879
Recruitment Status : Recruiting
First Posted : October 22, 2018
Last Update Posted : May 29, 2019
Sponsor:
Collaborators:
Xijing Hospital
Changhai Hospital
Tianjin Union Medical Center
Zhejiang University
Eastern Hepatobiliary Surgery Hospital
Information provided by (Responsible Party):
James Yun-wong Lau, Chinese University of Hong Kong

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.

Condition or disease Intervention/treatment Phase
Post ERCP Pancreatitis Device: pancreatic stenting Drug: Indomethacin Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1734 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  1. rectal indomethacin 100 mg to be administered before or after ERCP
  2. 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
  3. 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)
Primary Purpose: Prevention
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
Actual Study Start Date : March 21, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatitis

Arm Intervention/treatment
Experimental: indomethacin
rectal indomethacin 100 mg to be administered before or after ERCP
Drug: Indomethacin
rectally administered indomethacin before or after ERCP
Other Name: indocid

Experimental: pancreatic stenting
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)
Device: pancreatic stenting
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)

Experimental: indomethacin plus pancreatic stenting
[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]
Device: pancreatic stenting
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)

Drug: Indomethacin
rectally administered indomethacin before or after ERCP
Other Name: indocid




Primary Outcome Measures :
  1. post-ERCP pancreatitis [ Time Frame: 30 days ]
    Percentage of Participants with post ERCP pancreatitis

  2. high severity of post-ERCP pancreatitis [ Time Frame: 30 days ]

    Percentage of Participants with high severity of post-ERCP pancreatitis using the Clavian-Dindo classification

    (1 / 2 / 3 / 3a / 3b / 4 / 4a/ 4b / 5)


  3. pancreatitis with complications [ Time Frame: 30 days ]
    Percentage of Participants with pancreatitis with complications using Atlanta classification (Mild / Moderate / Severe / Critical )


Secondary Outcome Measures :
  1. hospital stay [ Time Frame: 30 days ]
    period of hospitalisation (days)

  2. endoscopic intervention due to PEP [ Time Frame: 30 days ]
    Percentage of Participants with endoscopic intervention due to Post ERCP pancreatitis

  3. radiologic intervention due to PEP [ Time Frame: 30 days ]
    Percentage of Participants with radiologic intervention due to Post ERCP pancreatitis

  4. surgery due to PEP [ Time Frame: 30 days ]
    Percentage of Participants with Surgical intervention due to Post ERCP pancreatitis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03713879


Contacts
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Contact: James LAU, MD 35051411 laujyw@surgery.cuhk.edu.hk
Contact: RAYMOND TANG, MD 35052640 raymondtang@cuhk.edu.hk

Locations
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China, Shan XI
Endoscopy centre Not yet recruiting
Xi'an, Shan XI, China, 710000
Contact: Yang Lin Pan, MD       panyl@fmmu.edu.cn   
Sub-Investigator: Pang Yang Lin, MD         
Principal Investigator: Kai Chun Wu, MD         
China, Shanghai
Endoscopy centre Not yet recruiting
Shanghai, Shanghai, China, 200000
Contact: Bing HU, MD       drhubing@aliyun.com   
Principal Investigator: Bing Hu, MD         
Endoscopy centre Not yet recruiting
Shanghai, Shanghai, China, 200000
Contact: Yu Bai, MD       baiyu1998@hotmail.com   
Principal Investigator: YU Bai, MD         
China, Tian Jin
Endoscopy centre Not yet recruiting
Tianjin, Tian Jin, China, 300000
Contact: Wen Li, MD       drliwen@126.com   
Principal Investigator: Wen Li, MD         
China, Zhejiang
Endoscopy centre Not yet recruiting
Hangzhou, Zhejiang, China, 310013
Contact: Yun Sheng Qing, MD       175260446@qq.com   
Principal Investigator: Yun sheng Qing, MD         
Hong Kong
Endoscopy Centre, Prince of Wales Hospital Recruiting
Hong Kong, Hong Kong
Contact: James Y LAU, Prof    +85235051411    laujyw@surgery.cuhk.edu.hk   
Sponsors and Collaborators
Chinese University of Hong Kong
Xijing Hospital
Changhai Hospital
Tianjin Union Medical Center
Zhejiang University
Eastern Hepatobiliary Surgery Hospital
Investigators
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Principal Investigator: James LAU, MD Chinese University of Hong Kong

Publications:

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Responsible Party: James Yun-wong Lau, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT03713879     History of Changes
Other Study ID Numbers: StentvsNSAID
First Posted: October 22, 2018    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by James Yun-wong Lau, Chinese University of Hong Kong:
post ERCP panceatitis
rectal indomethacin
pancreatic stents

Additional relevant MeSH terms:
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Pancreatitis
Pancreatic Diseases
Digestive System Diseases
Indomethacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gout Suppressants
Tocolytic Agents
Reproductive Control Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action