Trial Outcomes & Findings for Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin to Prevent Post-ERCP Pancreatitis (NCT NCT02116309)

Results Overview

The primary outcome variable of interest is the incidence of post ERCP pancreatitis (PEP) as defined by the consensus guidelines as 1) New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis and 2) amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure and 3) Hospitalization or prolongation of existing hospitalization for at least 2 days.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

948 participants

Primary outcome timeframe

24 hours after ERCP

Results posted on

2017-11-01

Participant Flow

We went above the goal sample size for enrollment as some of our centers had a few extra drug supplies available. Further, we allowed additional enrollment as it would strengthen data for our secondary objectives.

Participant milestones

Participant milestones
Measure	Rectal Indomethacin Only Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Overall Study STARTED	482	478
Overall Study COMPLETED	482	477
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Rectal Indomethacin Only Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rectal Indomethacin Only n=482 Participants Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine n=477 Participants Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine	Total n=959 Participants Total of all reporting groups
Age, Continuous	52.1 years STANDARD_DEVIATION 14.3 • n=5 Participants	52.5 years STANDARD_DEVIATION 15.6 • n=7 Participants	52.3 years STANDARD_DEVIATION 14.9 • n=5 Participants
Sex: Female, Male Female	275 Participants n=5 Participants	276 Participants n=7 Participants	551 Participants n=5 Participants
Sex: Female, Male Male	207 Participants n=5 Participants	201 Participants n=7 Participants	408 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours after ERCP

The primary outcome variable of interest is the incidence of post ERCP pancreatitis (PEP) as defined by the consensus guidelines as 1) New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis and 2) amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure and 3) Hospitalization or prolongation of existing hospitalization for at least 2 days.

Outcome measures

Outcome measures
Measure	Rectal Indomethacin Only n=482 Participants Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine n=477 Participants Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Number of Patients Who Developed Post-ERCP Pancreatitis	31 Participants	32 Participants

SECONDARY outcome

Timeframe: up to 30 days after ERCP

Severity of PEP defined using the consensus grading as Mild PEP that results in hospitalization (or prolongation of existing hospitalization) for ≤3 days. Moderate PEP will be defined as PEP that results in hospitalization (or prolongation of existing hospitalization) for 4-10 days. Severe PEP will be defined as PEP that results in hospitalization (or prolongation of existing hospitalization) for \> 10 days, or leads to the development of pancreatic necrosis or pseudocyst, or requires additional endoscopic, percutaneous, or surgical intervention.

Outcome measures

Outcome measures
Measure	Rectal Indomethacin Only n=482 Participants Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine n=477 Participants Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Number of Patients Who Developed Severe Post-ERCP Pancreatitis	4 Participants	7 Participants

Adverse Events

Rectal Indomethacin Only

Serious events: 1 serious events

Other events: 34 other events

Deaths: 3 deaths

Rectal Indomethacin Plus Papillary Spray of Epinephrine

Serious events: 1 serious events

Other events: 35 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Rectal Indomethacin Only n=482 participants at risk Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine n=477 participants at risk Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Cardiac disorders Arrythmia after ERCP	0.21% 1/482 • Number of events 1	0.00% 0/477
Gastrointestinal disorders Post sphincterotomy bleeding	0.00% 0/482	0.21% 1/477 • Number of events 1

Other adverse events

Other adverse events
Measure	Rectal Indomethacin Only n=482 participants at risk Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin	Rectal Indomethacin Plus Papillary Spray of Epinephrine n=477 participants at risk Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin. Rectal Indomethacin Epinephrine
Cardiac disorders Hypertension after ERCP	7.1% 34/482 • Number of events 34	7.3% 35/477 • Number of events 35

Additional Information

Dr. Vikesh Singh

Johns Hopkins University

Phone: 4106146708

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place