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

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01774604
• Collaborator: (none)
• Enrollment: 449
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 19.6

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether peri-procedural administration of rectal indomethacin, compared to placebo, can reduce the incidence of post-ERCP pancreatitis.

Condition or Disease	Intervention/Treatment	Phase
Post-ERCP Acute Pancreatitis	Drug: Indomethacin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 449 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Rectal Indomethacin to Prevent Post-ERCP Pancreatitis
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indomethacin Indomethacin 100 mg Per Rectum (PR) x 1 in peri-procedural period	Drug: Indomethacin; 100 mg Indomethacin PR x 1
Placebo Comparator: Placebo Placebo suppositories (#2)	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Developed Acute Pancreatitis [From randomization to 30 days after ERCP]

   Number of patients who developed pancreatitis following ERCP based on Atlanta Classification

Secondary Outcome Measures

1. Number of Patients Who Developed Severe Pancreatitis [From randomization to 30 days after ERCP]

   Number of patients with severe acute pancreatitis based on the Atlanta Classification

2. Number of Patients Who Developed Moderately Severe Pancreatitis [From randomization to 30 days after ERCP]

   Number of patients with moderately severe pancreatitis based on Atlanta Classification

3. Number of Patients Who Developed Mild Pancreatitis [From randomization to 30 days after ERCP]

   Number of patient who developed mild acute pancreatitis based on the Atlanta Classification

4. Number of Patients Who Developed Gastrointestinal Bleeding [From randomization to 30 days after ERCP]

   Number of patients who developed any type of gastrointestinal bleeding from time of ERCP to 30 days post procedure

5. Number of Patient Deaths [From randomization to 30 days after ERCP]

   Number of patients who died from any cause from the time of ERCP until 30 days post-procedure

6. Number of Patients With 30 Days Hospital Re-admission [From randomization until 30 days after ERCP]

   Number of patients admitted to the hospital for any cause following ERCP

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Scheduled for an ERCP at Dartmouth-Hitchcock

2. Age greater than 18 years old

3. Ability to provide written informed consent

Exclusion Criteria:

1. Inability to provide written informed consent

2. ERCP being performed for diagnosis and/or treatment of acute pancreatitis

3. Current ongoing acute pancreatitis

4. Previously documented allergy to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

5. Contra-indication to NSAID therapy (creatinine level >1.4 or active peptic ulcer disease), already taking NSAIDs (other than aspirin therapy for cardioprotection)

6. Pregnant or nursing mothers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: John M Levenick, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016 Apr;150(4):911-7; quiz e19. doi: 10.1053/j.gastro.2015.12.040. Epub 2016 Jan 9.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT01774604
• Other Study ID Numbers: CPHS#23749
• First Posted: Jan 24, 2013
• Last Update Posted: Nov 4, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Dartmouth-Hitchcock Medical Center: Post ERCP acute pancreatitis; Post Fine Needle Aspiration (FNA) acute pancreatitis; Indomethacin; Rectal Non Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Additional relevant MeSH terms: Pancreatitis; Indomethacin

Study Results

Participant Flow

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

Arm/Group Title	Indomethacin	Placebo
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

Baseline Characteristics

Arm/Group Title	Indomethacin	Placebo	Total
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 Participants	223	226	449
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (23.7)	64.3 (15.1)	64.6 (19.9)
Sex: Female, Male (Count of Participants)
Female	118 52.9%	118 52.2%	236 52.6%
Male	105 47.1%	108 47.8%	213 47.4%
Indication (participants) [Number]
Acute Cholangitis	12 5.4%	13 5.8%	25 5.6%
Choledocholithiasis	59 26.5%	52 23%	111 24.7%
Malignant Biliary Obstruction	53 23.8%	50 22.1%	103 22.9%
Biliary Stent Change	25 11.2%	25 11.1%	50 11.1%
Biliary Leak	11 4.9%	12 5.3%	23 5.1%
Increased Liver Tests/Jaundice	13 5.8%	9 4%	22 4.9%
Pancreatic Stricture	3 1.3%	5 2.2%	8 1.8%
Suspected Sphincter of Oddi Dysfunction (SOD)	6 2.7%	8 3.5%	14 3.1%
Pancreatic Leak/Disruption	11 4.9%	12 5.3%	23 5.1%
Pancreatic Duct Stone	3 1.3%	2 0.9%	5 1.1%
Recurrent Acute Pancreatitis	5 2.2%	2 0.9%	7 1.6%
Ampullectomy	6 2.7%	5 2.2%	11 2.4%
Other	16 7.2%	31 13.7%	47 10.5%
History of post-ERCP Pancreatitis (participants) [Number]
Yes	9 4%	9 4%	18 4%
No	214 96%	217 96%	431 96%
History of Previous Sphincterotomy (participants) [Number]
Yes	72 32.3%	71 31.4%	143 31.8%
No	151 67.7%	155 68.6%	306 68.2%
Previous ERCP (participants) [Number]
Yes	81 36.3%	79 35%	160 35.6%
No	142 63.7%	147 65%	289 64.4%
Difficult Cannulation (participants) [Number]
Yes	46 20.6%	42 18.6%	88 19.6%
No	177 79.4%	184 81.4%	361 80.4%
Precut Biliary Sphincterotomy (participants) [Number]
Yes	11 4.9%	16 7.1%	27 6%
No	212 95.1%	210 92.9%	422 94%
Therapeutic Biliary Sphincterotomy (participants) [Number]
Yes	106 47.5%	114 50.4%	220 49%
No	117 52.5%	112 49.6%	229 51%
Therapeutic Pancreatic Sphincterotomy (participants) [Number]
Yes	12 5.4%	5 2.2%	17 3.8%
No	211 94.6%	221 97.8%	432 96.2%
Minor Duct Sphincterotomy (participants) [Number]
Yes	5 2.2%	4 1.8%	9 2%
No	218 97.8%	222 98.2%	440 98%
Balloon Dilation of Biliary Sphincter (participants) [Number]
Yes	21 9.4%	20 8.8%	41 9.1%
No	202 90.6%	206 91.2%	408 90.9%
Wire Cannulation of Pancreatic Duct (participants) [Number]
Yes	90 40.4%	89 39.4%	179 39.9%
No	133 59.6%	137 60.6%	270 60.1%
Pancreatography (participants) [Number]
Yes	50 22.4%	49 21.7%	99 22%
No	173 77.6%	177 78.3%	350 78%
Pancreatic Acinarization (participants) [Number]
Yes	5 2.2%	4 1.8%	9 2%
No	218 97.8%	222 98.2%	440 98%
Biliary Strent Placement (participants) [Number]
Yes	89 39.9%	84 37.2%	173 38.5%
No	134 60.1%	142 62.8%	276 61.5%
Pancreatic Stent Placement (participants) [Number]
Yes	36 16.1%	35 15.5%	71 15.8%
No	187 83.9%	191 84.5%	378 84.2%
Trainee Involvement (participants) [Number]
Yes	152 68.2%	168 74.3%	320 71.3%
No	71 31.8%	58 25.7%	129 28.7%
Concomitant Endoscopic Ultrasound with Fine Needle Aspiration (EUS/FNA) (participants) [Number]
Yes	41 18.4%	40 17.7%	81 18%
No	182 81.6%	186 82.3%	368 82%
Periprocedural Fluid Volume (Milliliters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Milliliters]	705 (335)	703 (355)	704 (345)

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Developed Acute Pancreatitis
Description	Number of patients who developed pancreatitis following ERCP based on Atlanta Classification
Time Frame	From randomization to 30 days after ERCP

Outcome Measure Data

Analysis Population Description

Patient who randomized into the study and received either rectal indomethacin or placebo

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	16 7.2%	11 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Patients Who Developed Severe Pancreatitis
Description	Number of patients with severe acute pancreatitis based on the Atlanta Classification
Time Frame	From randomization to 30 days after ERCP

Outcome Measure Data

Analysis Population Description

Assess the number of patients who developed severe acute pancreatitis

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	0 0%	1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Patients Who Developed Moderately Severe Pancreatitis
Description	Number of patients with moderately severe pancreatitis based on Atlanta Classification
Time Frame	From randomization to 30 days after ERCP

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	0 0%	1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Number of Patients Who Developed Mild Pancreatitis
Description	Number of patient who developed mild acute pancreatitis based on the Atlanta Classification
Time Frame	From randomization to 30 days after ERCP

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	16 7.2%	9 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Number of Patients Who Developed Gastrointestinal Bleeding
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	4 1.8%	6 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Number of Patient Deaths
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	0 0%	3 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Number of Patients With 30 Days Hospital Re-admission
Description	Number of patients admitted to the hospital for any cause following ERCP
Time Frame	From randomization until 30 days after ERCP

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Placebo
Arm/Group Description	Indomethacin 100 mg PR x 1 in peri-procedural period Indomethacin: 100 mg Indomethacin PR x 1	Placebo suppositories (#2) Placebo
Measure Participants	223	226
Number [participants]	31 13.9%	20 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	From randomization to 30 days after ERCP
Arm/Group Title	Indomethacin		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indomethacin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/223 (0%)		3/226 (1.3%)
Gastrointestinal disorders
Severe Acute Pancreatitis Leading to Death	0/223 (0%)	0	1/226 (0.4%)	1
Secondary Bacterial Peritonitis due to Multifocal Hepatocellular Carcinoma Leading to Death	0/223 (0%)	0	1/226 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration Post-Procedure Leading to Death	0/223 (0%)	0	1/226 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Indomethacin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/223 (1.8%)		6/226 (2.7%)
Gastrointestinal disorders
Gastrointestinal Bleeding	4/223 (1.8%)	4	6/226 (2.7%)	6

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.