Rectal Indomethacin vs Intravenous Ketorolac

Study Overview
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Brief Summary
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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.

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

Conditions
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Post-ERCP Acute Pancreatitis

Intervention / Treatment
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* Drug: Rectal indomethacin
* Drug: IV ketorolac


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a prospective study where patients will be randomized into either rectal indomethacin or IV ketorolac.
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-ERCP Pancreatitis | Number of patient who develop 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed by FLACC or NRS scoring post ERCP | A minimum of 3 pain assessments are to be completed by nursing staff/anesthesia during admission: Anesthesia/ PACU- initial pain assessment Evening-2100- pain assessment by RN Morning -0800- pain assessment by RN 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 PEP (Amylase and Lipase) | Amylase (unit/L) Lipase (unit/L) | 2 weeks | 
| Length of stay |  | 2 weeks | 
| Severity of pancreatitis (mild, moderately severe, severe) | Severity of Acute Pancreatitis (AP): 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 that persists >48 hours. Persistent organ failure may be single or multiple, and may develop beyond the first 48 hours of presentation. | 2 weeks | 
| C-Reactive Protein (CRP) level | Measured in mg/dL | 2 weeks | 
| Post-ERCP bleeding |  | 2 weeks | 
| White Blood Cell | per/mcL | 2 weeks | 
| Red Blood Cell | per/mcL | 2 weeks | 
| Hemoglobin | gm/dL | 2 weeks | 
| Hematocrit |  | 2 weeks | 
| MCV | fL | 2 weeks | 
| MCH | pg | 2 weeks | 
| MCHC | gm/dL | 2 weeks | 
| RDW |  | 2 weeks | 
| PLATELET | per/mcL | 2 weeks |