Clinical trial NCT05832047: Aggressive Hydration With Lactated Ringer's Solution Versus Plasma Solution for the Prevention of Post ERCP Pancreatitis
Official title: Aggressive Hydration With Lactated Ringer's Solution Versus Plasma Solution for the Prevention of Post ERCP (Endoscopic Retrograde Cholangiopancreatography) Pancreatitis : Multicenter, Double Blind, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pancreatic Disease
Keywords: ERCP
Endoscopic retrograde cholangiopancreatography
Pancreatitis
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: HK inno.N Corporation
First posted: 2023-04-27
Enrollment: 844
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In the existing Aggressive hydration comparison study related to the prevention of post-ERCP pancreatitis (PEP), research bias may occur due to the lack of blinding between fluids, so in this study, the investigators will conduct a multicenter randomized comparative study in which the comparative fluids are double-blinded to observe differences between fluids in the preventive effect of pancreatitis that occurs after ERCP (endoscopic retrograde cholangiopancreatography).

A total of 844 patients scheduled for ERCP will be enrolled in this clinical trial and randomly assigned to the lactated Ringer's solution or to the Plasma solution in a 1:1 ratio. Eligible patients will receive study drug or control drug for up to 24 hours before and after ERCP implementation.

In previous comparative studies related to PEP prevention, research bias may have been introduced because of insufficient blinding of the treatment strategies, as well as instances where the evaluating investigator did not perform blinding. We are therefore conducting a multicenter, randomized comparative study double-blinded as to the two types of fluid (lactated Ringer's solution or plasma solution), and in which the endoscopists, outcome assessors and patients are blinded to the randomization allocation.

Detailed description: Post-ERCP pancreatitis (PEP), which occurs in 2% to 15% of all patients undergoing ERCP and is treated conservatively with fasting and sufficient fluid supply according to the standards of care for general acute pancreatitis, and most patients improve within a few days without major complications. However, high-risk patients are more susceptible to PEP with incidence rates between 15% and 42%, and severe pancreatitis can develop in 11.4% of PEP cases with a 3% mortality rate. Therefore, there are significant unmet needs for PEP patients.

In this trial, all patients will receive aggressive hydration involving fluids that are commercially available and widely administered. The trial aims to minimize potential risks and has established routine safety monitoring to protect the participants.

In real practice, it is crucial to consider not just the type of fluid utilized, but also the most effective fluid volume for preventing PEP, along with the optimal timing for administering the fluid. Given that a significant number of ERCPs are performed in outpatient settings in the USA and other countries, the current protocol allowing outpatients to occupy recovery areas for extended periods, such as 8 hours post-ERCP, seems challenging to implement in real clinical practice. These considerations highlight the necessity for a re-evaluation of existing guidelines. Therefore, the present reassessment aims, not only to optimize efficiency and patient flow in medical settings but also to evaluate the effectiveness of the protocol in preventing PEP considering practical duration of intravenous fluid infusion, such as 4 hours postprocedure.

Eligibility criteria: Inclusion Criteria:

Among patients with naive major duodenal papilla in patients, we will include those who are at average-to-high risk of PEP (if one or more of the following criteria) after ERCP and agree to enroll in this clinical trial.

1. 40 years of age or younger
2. (Suspected) Sphincter of oddi dysfunction
3. The normal level of serum total bilirubin
4. History of recurrent pancreatitis
5. Require injection of a contrast agent into the pancreatic duct
6. Require endoscopic biliary or pancreatic sphincterotomy
7. Require precut sphincterotomy
8. Require endoscopic papillary balloon dilation
9. Planned endoscopic papillectomy
10. Diagnosed with periampullary tumor and planned for insertion of a self-expanding metal stent

Exclusion Criteria:

Subjects are excluded if they meet any of the following items.

1. Not consented to study participation
2. 18 years of age or younger
3. Severe comorbidities (e.g., end-stage kidney disease, end-stage chronic obstructive pulmonary disease, hypoglycemic dysregulation, decompensated cirrhosis)
4. Sepsis (defined as meeting two or more of the following items):

   * Body temperature \>38.3ºC or \<36ºC
   * Heart rate \>90 beats/min
   * Tachypnea (respiratory rate \> 20 breaths/min)
   * Leukocytosis (WBC\>12,000/uL) or leukopenia (WBC\<4000/uL)
5. Acute pancreatitis
6. Chronic pancreatitis
7. Heart failure (NYHA class 2 or higher)
8. Clinical signs of fluid overload
9. Hypernatremia (\>150 mEq/L) or hyponatremia (\<130 mEq/L)
10. History of endoscopic sphincterotomy
11. History of endoscopic papillary (balloon) dilation
12. Hypercalcemia or alkalemia
13. Scheduled for regular endoscopic biliary stent change
14. Patients with pancreatic head tumors and a presumed low risk for pancreatitis
15. Lack of access to the major duodenal papilla due to surgically altered anatomy

Primary outcomes:
measure: Occurrence of pancreatitis after ERCP
timeFrame: the next morning or within 24 hours after ERCP
Secondary outcomes:
measure: Occurrence of pancreatitis after ERCP at 4 hours after ERCP
timeFrame: 4 hours after ERCP
measure: Number of Participants with Clinical signs of fluid overload
timeFrame: 4 hours and, and the next morning or within 24 hours after ERCP
measure: Number of Participants with Asymptomatic Hyperamylasemia
timeFrame: 4 hours and, the next morning or within 24 hours after ERCP
measure: Occurrence or aggravation of upper abdominal pain
timeFrame: 4 hours and, the next morning or within 24 hours after ERCP
measure: Days of ERCP-related hospital stay
timeFrame: Time for upper abdominal pain to disappear after the date of ERCP - up to 20 days
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Seoul Hopital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Asan Medical Center
name: Do Hyun Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: