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Rectal Indomethacin to Prevent Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01774604
Recruitment Status : Terminated (Futility)
First Posted : January 24, 2013
Results First Posted : September 20, 2016
Last Update Posted : November 4, 2016
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Post-ERCP Acute Pancreatitis
Interventions Drug: Indomethacin
Drug: Placebo
Enrollment 449
Recruitment Details All patients who presented to Dartmouth-Hitchcock Medical Center for Endoscopic Retrograde Cholangiopancreatography (ERCP) for any reason between March 2013 and December 2014
Pre-assignment Details  
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description

Indomethacin 100 mg Per Rectum (PR) x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Period Title: Overall Study
Started 223 226
Completed 223 226
Not Completed 0 0
Arm/Group Title Indomethacin Placebo Total
Hide Arm/Group Description

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 223 226 449
Hide Baseline Analysis Population Description
All patient randomized to receive rectal indomethacin or placebo
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 223 participants 226 participants 449 participants
64.9  (23.7) 64.3  (15.1) 64.6  (19.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Female
118
  52.9%
118
  52.2%
236
  52.6%
Male
105
  47.1%
108
  47.8%
213
  47.4%
Indication  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Acute Cholangitis 12 13 25
Choledocholithiasis 59 52 111
Malignant Biliary Obstruction 53 50 103
Biliary Stent Change 25 25 50
Biliary Leak 11 12 23
Increased Liver Tests/Jaundice 13 9 22
Pancreatic Stricture 3 5 8
Suspected Sphincter of Oddi Dysfunction (SOD) 6 8 14
Pancreatic Leak/Disruption 11 12 23
Pancreatic Duct Stone 3 2 5
Recurrent Acute Pancreatitis 5 2 7
Ampullectomy 6 5 11
Other 16 31 47
History of post-ERCP Pancreatitis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 9 9 18
No 214 217 431
History of Previous Sphincterotomy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 72 71 143
No 151 155 306
Previous ERCP  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 81 79 160
No 142 147 289
Difficult Cannulation   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 46 42 88
No 177 184 361
[1]
Measure Description: Difficult Cannulation was defined by >8 attempts at cannulation
Precut Biliary Sphincterotomy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 11 16 27
No 212 210 422
Therapeutic Biliary Sphincterotomy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 106 114 220
No 117 112 229
Therapeutic Pancreatic Sphincterotomy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 12 5 17
No 211 221 432
Minor Duct Sphincterotomy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 5 4 9
No 218 222 440
Balloon Dilation of Biliary Sphincter  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 21 20 41
No 202 206 408
Wire Cannulation of Pancreatic Duct  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 90 89 179
No 133 137 270
Pancreatography  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 50 49 99
No 173 177 350
Pancreatic Acinarization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 5 4 9
No 218 222 440
Biliary Strent Placement  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 89 84 173
No 134 142 276
Pancreatic Stent Placement  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 36 35 71
No 187 191 378
Trainee Involvement  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 152 168 320
No 71 58 129
Concomitant Endoscopic Ultrasound with Fine Needle Aspiration (EUS/FNA)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 223 participants 226 participants 449 participants
Yes 41 40 81
No 182 186 368
Periprocedural Fluid Volume  
Mean (Standard Deviation)
Unit of measure:  Milliliters
Number Analyzed 223 participants 226 participants 449 participants
705  (335) 703  (355) 704  (345)
1.Primary Outcome
Title Number of Patients Who Developed Acute Pancreatitis
Hide Description Number of patients who developed pancreatitis following ERCP based on Atlanta Classification
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
Patient who randomized into the study and received either rectal indomethacin or placebo
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
16 11
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Number of Patients Who Developed Severe Pancreatitis
Hide Description Number of patients with severe acute pancreatitis based on the Atlanta Classification
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
Assess the number of patients who developed severe acute pancreatitis
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
0 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Number of Patients Who Developed Moderately Severe Pancreatitis
Hide Description Number of patients with moderately severe pancreatitis based on Atlanta Classification
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
0 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients Who Developed Mild Pancreatitis
Hide Description Number of patient who developed mild acute pancreatitis based on the Atlanta Classification
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
16 9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Number of Patients Who Developed Gastrointestinal Bleeding
Hide Description Number of patients who developed any type of gastrointestinal bleeding from time of ERCP to 30 days post procedure
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
4 6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Number of Patient Deaths
Hide Description Number of patients who died from any cause from the time of ERCP until 30 days post-procedure
Time Frame From randomization to 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
0 3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Number of Patients With 30 Days Hospital Re-admission
Hide Description Number of patients admitted to the hospital for any cause following ERCP
Time Frame From randomization until 30 days after ERCP
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description:

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

Overall Number of Participants Analyzed 223 226
Measure Type: Number
Unit of Measure: participants
31 20
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Indomethacin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame From randomization to 30 days after ERCP
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Indomethacin Placebo
Hide Arm/Group Description

Indomethacin 100 mg PR x 1 in peri-procedural period

Indomethacin: 100 mg Indomethacin PR x 1

Placebo suppositories (#2)

Placebo

All-Cause Mortality
Indomethacin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Indomethacin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/223 (0.00%)      3/226 (1.33%)    
Gastrointestinal disorders     
Severe Acute Pancreatitis Leading to Death *  0/223 (0.00%)  0 1/226 (0.44%)  1
Secondary Bacterial Peritonitis due to Multifocal Hepatocellular Carcinoma Leading to Death *  0/223 (0.00%)  0 1/226 (0.44%)  1
Respiratory, thoracic and mediastinal disorders     
Aspiration Post-Procedure Leading to Death *  0/223 (0.00%)  0 1/226 (0.44%)  1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Indomethacin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/223 (1.79%)      6/226 (2.65%)    
Gastrointestinal disorders     
Gastrointestinal Bleeding * [1]  4/223 (1.79%)  4 6/226 (2.65%)  6
*
Indicates events were collected by non-systematic assessment
[1]
Patients with any type of gastrointestinal bleeding
The study was terminated due to indomethacin's lack of efficacy after 449 patients had been enrolled. Thus the study may be underpowered to draw conclusions about the role of indomethacin in preventing post ERCP pancreatitis
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John M. Levenick
Organization: Penn State Hershey Medical Center/Dartmouth-Hitchcock Medical Center
Phone: 603-667-1332
EMail: jlevenick@hmc.psu.edu
Layout table for additonal information
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01774604    
Other Study ID Numbers: CPHS#23749
First Submitted: January 21, 2013
First Posted: January 24, 2013
Results First Submitted: July 29, 2016
Results First Posted: September 20, 2016
Last Update Posted: November 4, 2016