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Aggressive Hydration With Lactated Ringer's Solution Versus Plasma Solution for the Prevention of Post ERCP Pancreatitis

Phase 4
Completed
Conditions
Pancreatic Disease
Interventions
Drug: Plasma solution (4-hour aggressive hydration)
Drug: Lactated Ringer solution (4-hour aggressive hydration)
Drug: 8-hour aggressive hydration
Registration Number
NCT05832047
Lead Sponsor
Do Hyun Park
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
844
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Plasma solutionPlasma solution (4-hour aggressive hydration)Plasma solution (HK inno.N Corp., Seoul, Republic of Korea) is a balanced crystalloid solution that contains the same ingredients as Plasma-Lyte A (Baxter International, Deer field, Ill) . Preprocedure hydration begins 30-90 min before ERCP with an infusion rate of 10 mL/kg. All the ERCP procedures are performed under sedation with balanced propofol sedation (incremental dose of propofol in combination with fixed doses of fentanyl and midazolam), without general anaesthesia. The infusion rate during ERCP and 30-60 min after ERCP is 3 mL/kg/hour and 10 mL/kg, respectively (in the case of a 10 mL/kg injection after the procedure, the injection should be stopped at the point where it is necessary to move from the endoscopy room to the ward after the procedure, and the injection rate can be changed to 3 mL/kg/hour).
Plasma solution8-hour aggressive hydrationPlasma solution (HK inno.N Corp., Seoul, Republic of Korea) is a balanced crystalloid solution that contains the same ingredients as Plasma-Lyte A (Baxter International, Deer field, Ill) . Preprocedure hydration begins 30-90 min before ERCP with an infusion rate of 10 mL/kg. All the ERCP procedures are performed under sedation with balanced propofol sedation (incremental dose of propofol in combination with fixed doses of fentanyl and midazolam), without general anaesthesia. The infusion rate during ERCP and 30-60 min after ERCP is 3 mL/kg/hour and 10 mL/kg, respectively (in the case of a 10 mL/kg injection after the procedure, the injection should be stopped at the point where it is necessary to move from the endoscopy room to the ward after the procedure, and the injection rate can be changed to 3 mL/kg/hour).
Lactated Ringer's solutionLactated Ringer solution (4-hour aggressive hydration)Preprocedure hydration begins 30-90 min before ERCP with an infusion rate of 10 mL/kg. All the ERCP procedures are performed under sedation with balanced propofol sedation (incremental dose of propofol in combination with fixed doses of fentanyl and midazolam), without general anaesthesia. The infusion rate during ERCP and 30-60 min after ERCP is 3 mL/kg/hour and 10 mL/kg, respectively (in the case of a 10 mL/kg injection after the procedure, the injection should be stopped at the point where it is necessary to move from the endoscopy room to the ward after the procedure, and the injection rate can be changed to 3 mL/kg/hour).
Lactated Ringer's solution8-hour aggressive hydrationPreprocedure hydration begins 30-90 min before ERCP with an infusion rate of 10 mL/kg. All the ERCP procedures are performed under sedation with balanced propofol sedation (incremental dose of propofol in combination with fixed doses of fentanyl and midazolam), without general anaesthesia. The infusion rate during ERCP and 30-60 min after ERCP is 3 mL/kg/hour and 10 mL/kg, respectively (in the case of a 10 mL/kg injection after the procedure, the injection should be stopped at the point where it is necessary to move from the endoscopy room to the ward after the procedure, and the injection rate can be changed to 3 mL/kg/hour).
Primary Outcome Measures
NameTimeMethod
Occurrence of pancreatitis after ERCPthe next morning or within 24 hours after ERCP

The new onset or worsening of pain in the upper abdomen, accompanied by an elevation of pancreatic enzymes to at least three times the upper normal level within 24 hours after the procedure, requiring hospitalization for a minimum of two nights.

Secondary Outcome Measures
NameTimeMethod
Days of ERCP-related hospital stayTime for upper abdominal pain to disappear after the date of ERCP - up to 20 days

Time for upper abdominal pain to disappear after the date of ERCP

Occurrence of pancreatitis after ERCP at 4 hours after ERCP4 hours after ERCP

The new onset or worsening of pain in the upper abdomen and the level of pancreatic enzymes is elevated\>3 times the upper limit of normal level after 4 hours after ERCP

Number of Participants with Clinical signs of fluid overload4 hours and, and the next morning or within 24 hours after ERCP

Clinical signs of fluid overload, for example, peripheral edema, pulmonary rales, increased jugular venous pressure, hepatojugular reflux, or both wll be monitored by investigator. If these signs are observed, hemodynamic testing or imaging studies will be done to investigate the evidence of pulmonary oedema, peripheral oedema, cardiac insufficiency and hypernatraemia.

Number of Participants with Asymptomatic Hyperamylasemia4 hours and, the next morning or within 24 hours after ERCP

Elevated level of serum amylase without upper abdominal pain

Occurrence or aggravation of upper abdominal pain4 hours and, the next morning or within 24 hours after ERCP

Occurrence or aggravation of upper abdominal pain

Trial Locations

Locations (3)

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Samsung Seoul Hopital

🇰🇷

Seoul, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

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