Tailored Hydration for the Prevention of Post-ERCP Pancreatitis

Study Overview
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Brief Summary
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Aggressive hydration of lactated Ringer's solution has shown considerable beneficial effect in preventing post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis. But the occurence rate of post-ERCP pancreatitis are near 10% and there are severe complications of aggressive hydration due to hypervolemia such pulmonary and peripheral edema, prolonged hospital stay and increased medical expense. Also there are no definite guidelines that suggest the duration and amount of hydration. This study evaluates the efficacy and safety of tailored hydration depending on each patient's condition that indicates the likelihood of developing post-ERCP pancreatitis.

Detailed Description
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ERCP(Endoscopic retrograde cholangiopancreatography) is the gold standard of diagnosis and treatment of pancreatobiliary disease. Pancreatitis is the most common complication after ERCP and can be lethally fatal. The most fundamental modality of preventing and treatment of post-ERCP pancreatitis is hydration and recent studies showed considerable preventive effect of aggressive hydration of lactated Ringer's solution. Lactated Ringer's solution has very low risk of adverse reaction and low cost compared to other preventive modalities such as octreotide, corticosteroids and protease inhibitors. Despite of these advantages of aggressive hydration of lactated Ringer's solution, the occurence rate of post-ERCP pancreatitis is near 10% and severe complications can develop due to hypervolemia caused by aggressive hydration such as pulmonary and peripheral edema, prolonged hospital stay and increased medical expense. Most of post-ERCP pancreatitis occur within several hours after ERCP and outpatients department based ERCP is suggested in some clinics by selecting patients with low risk of post-ERCP pancreatitis. A study compared the occurrence of post-ERCP pancreatitis between group with early feeding (4 hours after ERCP) and group with conventional feeding (24 hours after ERCP) and showed no difference. The most sensitive marker for predicting post-ERCP pancreatitis is abdominal pain and the occurrence time differs by whether endoscopic retrograde pancreatic duct (ERPD) stent insertion was performed or not. Patients without ERPD stent mostly develops abdominal pain at 2 hour after ERCP (0.5-2.5 hours) and patients with ERPD stent at 5 hour (0-68 hours). Also elevation of serum amylase level above 1.5 times the upper normal range after 4 hours of ERCP was suggested as useful marker for prediction of post-ERCP pancreatitis (AUROC 88.2%, 95% confidence interval 80.4%-90.6%). The effectiveness of hydration for preventing post-ERCP pancreatitis is widely accepted but there are no definite guidelines that suggest the duration and amount of hydration. Therefore, the purpose of this study is to evaluate the safety and efficacy of tailored hydration therapy based on markers that predicts the risk of post-ERCP pancreatitis development.

Official Title
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Tailored Hydration for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis

Conditions
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Cholangiopancreatography, Endoscopic Retrograde, Pancreatitis

Intervention / Treatment
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* Drug: Tailored aggressive hydration
* Drug: Tailored standard hydration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients older than 20 years undergoing ERCP for the 1st time will be recruited Exclusion Criteria: Age below 20 or above 80 years Underlying severe psychiatric illness Cardiac insufficiency (>New York Heart Association Class II heart failure) Renal insufficiency (eGFR <30mililiter/min/1.73m2) Respiratory insufficiency (defined as oxygen saturation < 90%) Poorly controlled blood sugar Ongoing hypotension including those with sepsis Ongoing acute pancreatitis Underlying disease of chronic pancreatitis Clinical signs of hypervolemia Hyponatremia (Na+ levels < 130 milliequivalent (mEq)/L)) Hypernatremia (Na+ levels > 150mEq/L) Hyperkalemia (5.1 mEq/dL) Metabolic alkalosis Past history of endoscopic sphincterectomy or endoscopic papillary balloon dilatation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tailored standard hydration<br>Patients will be randomly allocated to tailored standard hydration arm. Patients will receive hydration with lactated Ringer's solution with rate of 1.5 milliliter(mL)/kg/hr during and after ERCP. Hydration and feeding will be tailored by each patient's symptoms and serum amylase levels. | Drug: Tailored standard hydration<br>* Hydration with lactated Ringer's solution with rate of 1.5milliliter(mL)/kg/hr during and after ERCP. At 4 hours after ERCP (patients with ERPD stent insertion ; 6 hours), abdominal pain and serum amylase are checked. If pain (≥ Numeric rating scale (NRS) scale 3) is absent and amylase is below 1.5 times the UNL(upper normal limit), patient starts feeding and stops hydration. If patient has any of these signs, fasting and hydration continues. At 8 hours, if pain (<NRS scale 3) is absent, patient starts feeding and stops hydration. If patient has pain (≥ NRS scale 3) and previously checked amylase or re-checked serum amylase is above 3 times the UNL, patient is regarded as post-ERCP pancreatitis and receives 3mL/kg hydration. Patient with pain (≥ NRS scale 3) and previously checked serum amylase above 1.5 times but below 3 times the UNL, serum amylase is re-checked.<br>|
| Experimental: Tailored aggressive hydration<br>Patients will be randomly allocated to tailored aggressive hydration arm. Patients will receive hydration with lactated Ringer's solution with rate of 3.0 milliliter(mL)/kg/hr during and after ERCP and bolus injection of 20mL/kg over 1 hour after ERCP. Hydration and feeding will be tailored by each patient's symptoms and serum amylase levels. | Drug: Tailored aggressive hydration<br>* Hydration with lactated Ringer's solution with rate of 3.0 milliliter(mL)/kg/hr during and after ERCP and bolus injection of 20mL/kg for 1 hour after ERCP. At 4 hours after ERCP (patients with ERPD stent insertion ; 6 hours), abdominal pain and serum amylase are checked. If pain (≥ Numeric rating scale (NRS) scale 3) is absent and amylase is below 1.5 times the upper normal limit (UNL), patient starts feeding and stops hydration. If patient has any of these signs, fasting and hydration continues. At 8 hours, if pain (<NRS scale 3) is absent, patient starts feeding and stops hydration. If patient has pain (≥ NRS scale 3) and previously checked amylase or re-checked serum amylase is above 3 times the UNL, patient is regarded as post-ERCP pancreatitis and receives 3mL/kg hydration. Patient with pain (≥ NRS scale 3) and previously checked serum amylase above 1.5 times but below 3 times the UNL, serum amylase is re-checked.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of post-ERCP pancreatitis | Defined as pancreatic pain (≥ 3 on visual analogue numeric pain rating scale (0-10)) and serum amylase level 3 times the upper limit of normal. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical volume overload | Defined by physical findings of peripheral edema and pulmonary rales | 24 hours | 
| Hyperamylasemia | Elevated serum amylase level above than upper limit of normal | 24 hours | 
| Increased abdominal pain | Defined as an increase in abdominal pain based on the visual analogue numeric pain rating score (0-10) following the ERCP compared to the score immediately prior to the ERCP. | 24 hours | 
| Hospital stay | Whole duration of hospital admission days | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endoscopic retrograde pancreatocholangiography, Pancreatitis, Lactate ringer's solution, Tailored therapy