Trial Outcomes & Findings for SpHincterotomy for Acute Recurrent Pancreatitis (NCT NCT03609944)

Last Updated: 2025-12-30

Results Overview

To test this aim, compare the incidence of acute pancreatitis \> 30 days after treatment allocation as the primary outcome measure, using the next attack of acute pancreatitis as a time-to-event outcome.

Recruitment status

COMPLETED

Study phase

Target enrollment

181 participants

Primary outcome timeframe

This is a time-to-event outcome that is assessed starting 30 days after treatment through a maximum follow-up of 48 months.

Results posted on

2025-12-30

Participant Flow

Participant milestones

Participant milestones
Measure	EUS + Sham Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP With miES Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound
Overall Study STARTED	73	75
Overall Study COMPLETED	71	69
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	EUS + Sham Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP With miES Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound
Overall Study Lost to Follow-up	1	5
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

SpHincterotomy for Acute Recurrent Pancreatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EUS + Sham n=73 Participants Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP With miES n=75 Participants Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound	Total n=148 Participants Total of all reporting groups
Age, Continuous	52 Years n=174 Participants	56 Years n=166 Participants	54 Years n=167 Participants
Sex: Female, Male Female	52 Participants n=174 Participants	49 Participants n=166 Participants	101 Participants n=167 Participants
Sex: Female, Male Male	21 Participants n=174 Participants	26 Participants n=166 Participants	47 Participants n=167 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=174 Participants	3 Participants n=166 Participants	7 Participants n=167 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=174 Participants	71 Participants n=166 Participants	137 Participants n=167 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=174 Participants	1 Participants n=166 Participants	4 Participants n=167 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=174 Participants	1 Participants n=166 Participants	1 Participants n=167 Participants
Race (NIH/OMB) Asian	1 Participants n=174 Participants	1 Participants n=166 Participants	2 Participants n=167 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=174 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants
Race (NIH/OMB) Black or African American	6 Participants n=174 Participants	5 Participants n=166 Participants	11 Participants n=167 Participants
Race (NIH/OMB) White	65 Participants n=174 Participants	64 Participants n=166 Participants	129 Participants n=167 Participants
Race (NIH/OMB) More than one race	0 Participants n=174 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=174 Participants	4 Participants n=166 Participants	5 Participants n=167 Participants

PRIMARY outcome

Timeframe: This is a time-to-event outcome that is assessed starting 30 days after treatment through a maximum follow-up of 48 months.

Outcome measures

Outcome measures
Measure	EUS + Sham n=73 Participants Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP with miES n=75 Participants Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound
Reduce the Risk of Subsequent Acute Pancreatitis Episodes by 33%	32 Participants	26 Participants

SECONDARY outcome

Timeframe: Incidence rate will be assessed starting 30 days after treatment through a maximum follow-up of 48 months.

All randomized subjects will be followed longitudinally until study completion (minimum follow-up of six months, maximum follow-up of 48 months), even if acute pancreatitis occurs during follow-up. A secondary benefit of miES may be a reduction in acute pancreatitis frequency, defined as the incidence rate (episodes/time pre- and post-randomization). Since baseline incidence rate is a probable predictor of post-randomization incidence rate, the investigators will compare the incidence rate ratios between the two arms, keeping person-time equal between the pre/post periods.

Outcome measures

Outcome measures
Measure	EUS + Sham n=73 Participants Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP with miES n=75 Participants Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound
To Compare the Incidence Rate Ratio of Acute Pancreatitis Between Treatment Groups	0.304 Incidence rate ratio Interval 0.226 to 0.411	.246 Incidence rate ratio Interval 0.178 to 0.34

Adverse Events

EUS + Sham

Serious events: 48 serious events

Other events: 8 other events

Deaths: 3 deaths

EUS + ERCP With miES

Serious events: 48 serious events

Other events: 15 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Gregory Cote

Oregon Health and Science University

Phone: 503-494-4373

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	EUS + Sham n=73 participants at risk Subjects randomized to EUS + sham will undergo a diagnostic endoscopic ultrasound (EUS) under sedation. The physician investigator will not make any attempts to achieve minor papilla cannulation, but photo document the minor papilla using a duodenoscope. Diluted dye will be injected into the duodenum. A small caliber prophylactic pancreatic duct stent will be deposited into the duodenal lumen. These maneuvers are performed to minimize the risk of unmasking. EUS: Endoscopic ultrasound	EUS + ERCP With miES n=75 participants at risk Subjects randomized to EUS + ERCP with miES will undergo the procedure at the same time as endoscopic ultrasound (EUS), under sedation. Indomethacin (100 mg) will be administered rectally at the onset of the ERCP procedure in patients with no known allergy to indomethacin. The techniques used to perform the endoscopic retrograde cholangiopancreatography (ERCP)with miES (minor papilla endoscopic sphincterotomy) will be left to the discretion of the study endoscopist. The extent of sphincterotomy will be per the discretion of the treating endoscopist. Unless methylene blue (or similar chromoendoscopy agent such as indigo carmine) has already been used to facilitate minor papilla cannulation, diluted dye will be injected into the duodenum. ERCP with miES: Endoscopic retrograde cholangiopancreatography with minor papilla endoscopic sphincterotomy EUS: Endoscopic ultrasound
General disorders Missing	2.7% 2/73 • Number of events 2 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	2.7% 2/75 • Number of events 2 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Gastrointestinal disorders Abdominal pain	5.5% 4/73 • Number of events 4 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	9.3% 7/75 • Number of events 7 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Gastrointestinal disorders Constipation	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	2.7% 2/75 • Number of events 2 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Gastrointestinal disorders Nausea	1.4% 1/73 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	2.7% 2/75 • Number of events 2 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Gastrointestinal disorders Vomiting	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
General disorders and administration site conditions Pyrexia	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Infections and infestations Cellulitis	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Infections and infestations Folliculitis	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Infections and infestations Pneumonia	1.4% 1/73 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	0.00% 0/75 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Injury, poisoning and procedural complications Post procedural constipation	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.4% 1/73 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	0.00% 0/75 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/73 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.	1.3% 1/75 • Number of events 1 • Serious adverse events were collected from randomization through the end of the 48-month study period. Non-serious adverse events were collected from randomization through Day 30.