Rectal Indomethacin vs Intravenous Ketorolac

Post ERCP Pancreatitis Prophylaxis, Effectiveness of Rectal Indomethacin vs Intravenous Ketorolac in the Pediatric Population

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure that can be complicated by post-ERCP pancreatitis (PEP). Indomethacin and ketorolac are two medications used to prevent PEP. The main reason for this research study is to compare the effectiveness these drugs at reducing rates of PEP. There have been no studies comparing the effectiveness of these medications in preventing PEP in pediatric patients. You are being asked to take part in this research study because you are scheduled to have an ERCP as part of your medical care.

Study Overview

• Status: Completed
• Conditions: Post-ERCP Acute Pancreatitis
• Intervention / Treatment: Drug: Rectal indomethacin; Drug: IV ketorolac

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any patient undergoing ERCP (diagnostic or therapeutic with cannulation of the major or minor papilla)
• Age 6 month- 21 years old
• Does not meet exclusion criteria

Exclusion Criteria:

• < 10 kg
• Low risk subgroup: Biliary indication with history of prior biliary sphincterotomy.
• High risk for bleeding (Example: Planned liver biopsy)
• Gastrointestinal bleeding in previous 3 days
• Acute pancreatitis (within 3 days) at the time of ERCP
• Use of NSAIDs in the previous 5 days
• Peptic ulcer disease
• Acute kidney Injury or Known Chronic Kidney Disease per KDIGO
• Pregnancy (Pregnancy tests are administered prior to ERCP as standard of care)
• Lithium therapy
• Allergy to ketorolac or indomethacin
• Organ Dysfunction or SIRS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rectal indomethacin; Dosage based on subject's weight: >=50 kg, 100 mg; 30-49 kg, 50 mg; 10-29 kg, 25 mg	Drug: Rectal indomethacin; Dosage based on subject's weight: >=50 kg, 100 mg; 30-49 kg, 50 mg; 10-29 kg, 25 mg
Experimental: IV ketorolac; Dosage based on subject's weight: 0.5 mg/kg (maximum: 15 mg)	Drug: IV ketorolac; Dosage based on subject's weight: 0.5 mg/kg (maximum: 15 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-ERCP Pancreatitis	Below is the number of participants within the rectal indomethacin and IV ketorolac cohorts who developed Post-ERCP Pancreatitis- Post ERCP Pancreatitis: A patient must have at least 2 of the following to establish a diagnosis of post ERCP pancreatitis: Characteristic physical exam findings- pain worse than admission per pain scales (please see point 2) and/or nausea; Amylase (unit/L) or lipase(unit/L) greater than 3 times the age appropriate upper limit of normal.Normal range of amylase (15-127 unit/L)Normal range of lipase (12-50 unit/L); Confirmatory imaging (Ultrasound, CT or MRI) that suggests or demonstrates pancreatic inflammation	2 weeks
Post-ERCP Pancreatitis: Pancreatic Duct Injections	86 participants from the rectal indomethacin cohort and 83 from IV ketorolac received pancreatic duct injections during their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who received pancreatic duct injections.	2 weeks
Post-ERCP Pancreatitis: Native Papilla	36 participants from the rectal indomethacin cohort and 33 from IV ketorolac had a native papilla for their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who had a native papilla.	2 weeks
Post-ERCP Pancreatitis: Pancreatic Sphincterotomy	25 participants from the rectal indomethacin cohort and 19 from IV ketorolac received pancreatic sphincterotomies during their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who received pancreatic sphincterotomies.	2 weeks
Post-ERCP Pancreatitis: Opti-Ray Amount	83 participants from the rectal indomethacin cohort and 84 from IV ketorolac received various amounts of Opti-Ray during their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who received Opti-Ray.	2 weeks
Post-ERCP Pancreatitis: Therapeutic Pancreatic Duct Stent Placed	51 participants from the rectal indomethacin cohort and 53 from IV ketorolac received a therapeutic pancreatic duct stent during their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who received therapeutic pancreatic duct stents.	2 weeks
Post-ERCP Pancreatitis: Prophylactic Pancreatic Duct Stent Placed	11 participants from the rectal indomethacin cohort and 11 from IV ketorolac received a prophylactic pancreatic duct stent during their ERCP. Below we describe the outcome measure of post-ERCP pancreatitis vs. no pancreatitis for those who received prophylactic pancreatic duct stents.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Assessed by FLACC or NRS Scoring Post ERCP: PACU	A minimum of 3 pain assessments were completed by nursing staff/anesthesia during admission: Anesthesia/ PACU- initial pain assessment Evening-2100- pain assessment by RN Morning -0800- pain assessment by RN We defined *Pain score > 0 (any pain) for patients in the rectal indomethacin vs. IV ketorolac cohorts using the NRS and FLACC Pain scale. Face, Legs, Activity, Cry, and Consolability (FLACC) Pain scale for patients 0-5 years of age and patients unable to verbalize pain Numeric Rating Scale (NRS) Pain scale for patients 6 years old and above; Mild- 0 to 3; Moderate- 4 to 6; Severe- 7 to 10	2 weeks
Pain Assessed by FLACC or NRS Scoring Post ERCP: Evening	Not all patients were admitted following the procedure which accounts for the difference in overall number of participants analyzed. A minimum of 3 pain assessments were completed by nursing staff/anesthesia during admission: Anesthesia/ PACU- initial pain assessment Evening-2100- pain assessment by RN Morning -0800- pain assessment by RN We defined *Pain score > 0 (any pain) for patients in the rectal indomethacin vs. IV ketorolac cohorts using the NRS and FLACC Pain scale. Face, Legs, Activity, Cry, and Consolability (FLACC) Pain scale for patients 0-5 years of age and patients unable to verbalize pain Numeric Rating Scale (NRS) Pain scale for patients 6 years old and above; Mild- 0 to 3; Moderate- 4 to 6; Severe- 7 to 10	2 weeks
Pain Assessed by FLACC or NRS Scoring Post ERCP: Morning	Not all patients were admitted following the procedure which accounts for the difference in overall number of participants analyzed. A minimum of 3 pain assessments were completed by nursing staff/anesthesia during admission: Anesthesia/ PACU- initial pain assessment Evening-2100- pain assessment by RN Morning -0800- pain assessment by RN We defined *Pain score > 0 (any pain) for patients in the rectal indomethacin vs. IV ketorolac cohorts using the NRS and FLACC Pain scale. Face, Legs, Activity, Cry, and Consolability (FLACC) Pain scale for patients 0-5 years of age and patients unable to verbalize pain Numeric Rating Scale (NRS) Pain scale for patients 6 years old and above; Mild- 0 to 3; Moderate- 4 to 6; Severe- 7 to 10	2 weeks
Laboratory Markers Associated With PEP ( Lipase)	Lipase (unit/L)	2 weeks
Laboratory Markers Associated With PEP (Amylase)	Amylase value in unit/L	2 weeks
Length of Stay	Below is the median length of stay for participants within the rectal indomethacin and IV ketorolac cohorts. The difference in participants analyzed is due to the fact that not all participants were admitted following the procedure.	2 weeks
Severity of Pancreatitis (Mild, Moderately Severe, Severe)	Severity of AP will be classified as mild, moderately severe, or severe in accordance with the NASPGHAN Classification system.; Mild: "AP that is not associated with any organ failure, local or systemic complications, and usually resolves within the first week after presentation."; Moderately Severe: "AP with either the development of transient organ failure/dysfunction (lasting no >48 hours) or development of local or systemic complications. Local complications would include development of (peri) or pancreatic complications including fluid collections or necrosis. Systemic complications would include exacerbation of previously diagnosed co-morbid disease (such as lung disease or kidney disease)."; Severe: "AP with development of organ dysfunction per International pediatric sepsis consensus conference (please see definition 9) that persists >48 hours. Persistent organ failure may be single or multiple, and may develop beyond the first 48 hours of presentation."	2 weeks

Collaborators and Investigators

• Sponsor: David Vitale MD
• Investigators: Principal Investigator: David Vitale, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indomethacin; Indoles; Ketorolac
• Other Study ID Numbers: 2022-0640

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No