Trial Outcomes & Findings for Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis (NCT NCT01912716)

NCT ID: NCT01912716

Last Updated: 2019-07-05

Results Overview

Assessment of whether patients developed post-ERCP pancreatitis, defined as a new onset of pain (or worsening of existing pain) in the upper abdomen, an elevation in pancreatic enzymes of at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least two nights.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

1037 participants

Primary outcome timeframe

5 days

Results posted on

2019-07-05

Participant Flow

Patients were recruited between July 2013 - March 2018, either from the ERCP (Endoscopic Retrograde Cholangiopancreatography) outpatient clinic or Peri-Operative Care Unit immediately prior to ERCP.

Participant milestones

Participant milestones
Measure	High-dose Indomethacin 200mg rectal indomethacin high dose indomethacin	Standard Dose Indomethacin 100mg rectal indomethacin standard dose
Overall Study STARTED	522	515
Overall Study Receipt of 2nd Dose	511	503
Overall Study 5-day Follow-up	522	515
Overall Study 3-day Follow-up	521	513
Overall Study COMPLETED	522	515
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Dose Group n=515 Participants Participants randomized to this group receive 100 mg indomethacin	High Dose Group n=522 Participants Participants randomized to this group receive 200 mg indomethacin	Total n=1037 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 15.2 • n=5 Participants	50.4 years STANDARD_DEVIATION 15 • n=7 Participants	49.9 years STANDARD_DEVIATION 15.1 • n=5 Participants
Sex: Female, Male Female	392 Participants n=5 Participants	421 Participants n=7 Participants	813 Participants n=5 Participants
Sex: Female, Male Male	123 Participants n=5 Participants	101 Participants n=7 Participants	224 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	15 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	493 Participants n=5 Participants	507 Participants n=7 Participants	1000 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) White	485 Participants n=5 Participants	501 Participants n=7 Participants	986 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
BMI	28.6 kg/m^2 STANDARD_DEVIATION 7.0 • n=5 Participants	29.2 kg/m^2 STANDARD_DEVIATION 7.6 • n=7 Participants	28.9 kg/m^2 STANDARD_DEVIATION 7.3 • n=5 Participants
Obese	193 Participants n=5 Participants	198 Participants n=7 Participants	391 Participants n=5 Participants
Clinical Suspicion of SOD (sphincter of Oddi dysfunction)	319 Participants n=5 Participants	331 Participants n=7 Participants	650 Participants n=5 Participants
History of post-ERCP pancreatitis	77 Participants n=5 Participants	100 Participants n=7 Participants	177 Participants n=5 Participants
History of recurrent pancreatitis	202 Participants n=5 Participants	210 Participants n=7 Participants	412 Participants n=5 Participants
Difficult Cannulation	148 Participants n=5 Participants	146 Participants n=7 Participants	294 Participants n=5 Participants
Precut sphincterotomy	71 Participants n=5 Participants	46 Participants n=7 Participants	117 Participants n=5 Participants
Double-wire cannulation technique	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Pancreatography (patients)	446 Participants n=5 Participants	433 Participants n=7 Participants	879 Participants n=5 Participants
Number of pancreatic duct injections	2.12 injections STANDARD_DEVIATION 1.63 • n=5 Participants	1.96 injections STANDARD_DEVIATION 1.66 • n=7 Participants	2.04 injections STANDARD_DEVIATION 1.64 • n=5 Participants
Therapeutic pancreatic sphincterotomy	245 Participants n=5 Participants	231 Participants n=7 Participants	476 Participants n=5 Participants
Placement of pancreatic stent	400 Participants n=5 Participants	393 Participants n=7 Participants	793 Participants n=5 Participants
Ampullectomy	30 Participants n=5 Participants	32 Participants n=7 Participants	62 Participants n=5 Participants
Biliary sphincterotomy	302 Participants n=5 Participants	290 Participants n=7 Participants	592 Participants n=5 Participants
Trainee involvement	84 Participants n=5 Participants	68 Participants n=7 Participants	152 Participants n=5 Participants

PRIMARY outcome

Timeframe: 5 days

Outcome measures

Outcome measures
Measure	Standard 100mg Dose n=515 Participants patients receiving 100mg indomethacin	High Dose 200 mg n=522 Participants patients receiving 200mg indomethacin
Number of Participants Who Developed Post-ERCP Pancreatitis	76 Participants	65 Participants

SECONDARY outcome

Timeframe: 30 days

Population: development of moderate or severe post-ERCP pancreatitis

Assessment of whether patients developed either moderate or severe post-ERCP pancreatitis, defined according to established consensus criteria (Cotton et al., Gastrointestinal Endoscopy 1991;37:383-93). Severity of post-ERCP pancreatitis is partly defined according to length of stay. Moderate pancreatitis is defined as a 4-10 day hospitalization. Severe post-ERCP pancreatitis is defined as a hospitalization of greater than 10 days post-ERCP, or development of a complication (eg. pseudocyst or necrosis), or need for intervention (drainage or surgery).

Outcome measures

Outcome measures
Measure	Standard 100mg Dose n=515 Participants patients receiving 100mg indomethacin	High Dose 200 mg n=522 Participants patients receiving 200mg indomethacin
Number of Participants With Moderate or Severe Post-ERCP Pancreatitis	28 Participants	28 Participants

Adverse Events

Standard-dose Indomethacin

Serious events: 83 serious events

Other events: 0 other events

Deaths: 0 deaths

High-dose Indomethacin

Serious events: 77 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard-dose Indomethacin n=515 participants at risk 100mg rectal indomethacin standard dose indomethacin	High-dose Indomethacin n=522 participants at risk 200mg rectal indomethacin high-dose dose
Gastrointestinal disorders pancreatitis	14.8% 76/515 • Number of events 76 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	12.5% 65/522 • Number of events 65 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.
Gastrointestinal disorders bleeding	1.2% 6/515 • Number of events 6 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	1.5% 8/522 • Number of events 8 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.
Renal and urinary disorders renal failure	0.00% 0/515 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	0.57% 3/522 • Number of events 3 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.
Cardiac disorders myocardial infarction	0.19% 1/515 • Number of events 1 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	0.00% 0/522 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.
Nervous system disorders transient ischaemic attack	0.00% 0/515 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	0.19% 1/522 • Number of events 1 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.
Immune system disorders allergy	0.00% 0/515 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.	0.00% 0/522 • Adverse event data were collected throughout the length of the study, i.e. 5 years. Patients were recruited from July 2013 until March 2018. Following recruitment of the last patient (i.e. #1037), follow-up for an additional 30-day period was undertaken to capture severity of pancreatitis (should it occur) and delayed adverse events. In this study, there was no difference in definition of adverse events or serious adverse events, as other \[not including serious\] adverse events were not monitored/assessed. All patients provided contact information (home phone, cell phone, personal e-mail address) at study entry, and patients were then contacted at 5 and 30 days to assess for these adverse events, as noted in the study protocol.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Evan Fogel

Indiana University

Phone: 317-944-2816

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place