Clinical trial NCT02308891: A Prospective Trial of Aggressive Hydration Strategy to Reduce Post-ERCP Pancreatitis
Official title: Multicenter Prospective Randomized Trial of Aggressive Hydration Strategy to Reduce Post-ERCP Pancreatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post-ERCP Acute Pancreatitis
Keywords: pancreatitis
ERCP
Lead sponsor: Dankook University
Sponsor class: OTHER
Collaborators: name: Wonkwang University
name: University of Ulsan
First posted: 2014-12-04
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Postendoscopic retrograde cholangiopancreatography pancreatitis is the most frequent and serious complication of ERCP procedures, occurring in approximately 5-15% of unselected patients. Pharmacologic prevention of post-ERCP pancreatitis has been the topic of several investigations in recent years. Hydration is considered a mainstay of treatment for acute pancreatitis. We perform multicenter, prospective, randomized trial to investigate whether intravenous vigorous hydration with lactated Ringer's solution reduces the risk of post-ERCP pancreatitis.

Inclusion criteria : consecutive patients older than 18 years who are scheduled to undergo diagnostic or therapeutic ERCP will be recruited.

Patients will be randomly assigned in a 1:1 ratio to receive either vigorous hydration (treatment arm) or standard hydration (standard arm). Randomization will be performed in a double blinded fashion using computer-generated random numbers.

Treatment arm (vigorous hydration arm);

* Initial bolus of lactated Ringer's solution at 10 mL/kg over 1 hour prior to ERCP
* Intravenous lactated Ringer's solution at a rate of 3 mL/kg/h during the procedure and continued for 8 hours.
* At the end of ERCP, post-procedure bolus of lactated Ringer's solution at 10 mL/Kg over 1hour Standard arm (standard hydration arm);
* Patients will receive lactated Ringer's solution at the start of the ERCP and the fluids will be administered at a rate of 1.5 ml/kg/h during the procedure and for 8hours after ERCP.

The primary endpoint was development of post-ERCP pancreatitis, which define as increased pancreatic pain (more than 3 on a visual analogue pain scale) and hyperamylasemia (three times the upper limit of normal).

The secondary endpoint included the development of asymptomatic hyperamylasemia, severity of pancreatitis, and fluid overload.

Detailed description: Postendoscopic retrograde cholangiopancreatography pancreatitis is the most frequent and serious complication of ERCP procedures, occurring in approximately 5-15% of unselected patients. Pharmacologic prevention of post-ERCP pancreatitis has been the topic of several investigations in recent years. Hydration is considered a mainstay of treatment for acute pancreatitis. We perform multicenter, prospective, randomized trial to investigate whether intravenous vigorous hydration with lactated Ringer's solution reduces the risk of post-ERCP pancreatitis.

Patients will be randomly assigned in a 1:1 ratio to receive either vigorous hydration (treatment arm) or standard hydration (standard arm). Randomization will be performed in a double blinded fashion using computer-generated random numbers.

Treatment arm (vigorous hydration arm);

* Initial bolus of lactated Ringer's solution at 10 mL/kg over 1 hour prior to ERCP
* Intravenous lactated Ringer's solution at a rate of 3 mL/kg/h during the procedure and continued for 8 hours.
* At the end of ERCP, post-procedure bolus of lactated Ringer's solution at 10 mL/Kg over 1 hour

Standard arm (standard hydration arm);

- Patients will receive lactated Ringer's solution at the start of the ERCP and the fluids will be administered at a rate of 1.5 ml/kg/h during the procedure and for 8hours after ERCP.

The primary endpoint is development of post-ERCP pancreatitis, which define as increased pancreatic pain (more than 3 on a visual analogue pain scale) and hyperamylasemia (three times the upper limit of normal).

The secondary endpoint included the development of asymptomatic hyperamylasemia, severity of pancreatitis, and fluid overload.

Serum amylase levels are measured at baseline, and at 8 hours and 18-24 hours, 48 hours after the procedure.

Investigators recorded the details of the maneuvers performed, including:

1. the total time of the procedure,
2. the number of attempts at cannulation,
3. the number of pancreatic duct cannulation,
4. the final diagnosis by ERCP,
5. whether a sphincterotomy, a needle-knife papillotomy, or stent placement
6. endoscopic papillary balloon dilation,
7. common bile duct (C) tissue sampling (biopsy, brush, cytology),
8. common bile duct-intraductal ultrasonography (C-IDUS),

   * Serum amylase is determined 8, 18\~24, and 48 hours after ERCP.

     * If the 12-hours serum amylase level was \> 3 times the upper normal limit and the patient exhibited pain or nausea and vomiting, then the patient had pancreatitis.
     * Acute pancreatitis is defined as serum amylase \> 3 times the upper limit of normal and associated with epigastric pain, back pain, and epigastric tenderness.
   * Statistical analysis:

     1. Randomization was done by the GI nurse, concealed envelop
     2. Data were summarized by descriptive statistics.
     3. The Chi square was used to compare categorical patient data.
     4. The Student's t test was used to compare continuous variables.
     5. Two-tailed P \< 0.05 was considered to indicate significance.

Eligibility criteria: Inclusion Criteria:

* consecutive patients older than 18 years who are scheduled to undergo diagnostic or therapeutic ERCP will be recruited

Exclusion Criteria:

* Patients will be excluded if they have acute pancreatitis during the 2 weeks before ERCP, a history of chronic pancreatitis, previous sphincterotomy, or if they refuse to participate the study protocol. Patients will be also excluded if they undergo ERCP, for procedures such as stone removal following previous sphincterotomy, change or removal of previous biliary stents, or surveillance biopsy after endoscopic papillectomy without pancreatography, which are considered to carry minimal risks of post-ERCP pancreatitis. Patients with high risk of fluid overload (heart failure, more than NYHA II; renal insufficiency, creatinine clearance \<40ml/min; liver cirrhosis; or hypoxemia, SaO2 \<90%; signs of pulmonary edema) are excluded.

Primary outcomes:
measure: development of post-ERCP pancreatitis
timeFrame: 48 hours
Secondary outcomes:
measure: development of hyperamylasemia
timeFrame: 48 hours
measure: severity of pancreatitis
timeFrame: 3 months
measure: any signs of fluid overload
timeFrame: 48 hours
Other outcomes:
Locations:
city: Cheonan
country: Korea, Republic of
facility: Dankook University College of Medicine
state: Chungcheongnam-do
city: Iksan
country: Korea, Republic of
facility: Wonkwang University
state: Jeollabukdo
city: Ulsan
country: Korea, Republic of
facility: University of Ulsan, Ulsa University Hospital
Study officials:
affiliation: Dankook University College of Medicine
name: Jun Ho Choi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Choi JH, Kim HJ, Lee BU, Kim TH, Song IH. Vigorous Periprocedural Hydration With Lactated Ringer's Solution Reduces the Risk of Pancreatitis After Retrograde Cholangiopancreatography in Hospitalized Patients. Clin Gastroenterol Hepatol. 2017 Jan;15(1):86-92.e1. doi: 10.1016/j.cgh.2016.06.007. Epub 2016 Jun 14.