Examination of post-ERCP pancreatitis preventive effect of load infusion therapy with lactated Ringer's solution Randomized controlled trial

JRCT ID: jRCTs031200202

Registered date:16/11/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Biliary-pancreatic diseases for which ERCP is indicated
• Date of first enrollment: 25/03/2021
• Target sample size: 950
• Study type: Interventional

Intervention(s)

The effective initial treatment for acute pancreatitis is infusion therapy with extracellular fluid such as lactated Ringer's from the viewpoint of maintaining pancreatic microcirculation during inflammation. Although there have been reports of verifying the pancreatitis onset suppressive effect in patients with low risk of post-ERCP pancreatitis by rapid fluid infusion during ERCP, it was confirmed that the post-ERCP pancreatitis was moderately associated with NSAIDs use cases and pancreatic duct stent execution cases. There are no reports that examined a large number of patients who were at risk of illness or higher. This time, we will examine the effect of preventing pancreatitis onset and suppressing the severity of pancreatitis by securing a sufficient fluid volume during the perioperative period of ERCP.

Test treatment: Loaded infusion group
The rationale for the study treatment to be effective in the target disease (mechanism and review of previous studies): Effective treatment of acute pancreatitis is a large volume infusion from the viewpoint of maintaining pancreatic microcirculation during inflammation. Although there are reports that verified the effect of rapid infusion (3.0 ml/kg/h) during ERCP on pancreatitis onset in patients with low risk of post-ERCP pancreatitis, it is related to NSAIDs use cases and pancreatic duct stent execution cases. In addition, there are no reports of studies in a large number of patients with moderate or higher risk of post-ERCP pancreatitis.

Evidence that study treatment may be superior to control treatment: One of the important treatments for pancreatitis is high volume infusion. Lactate Ringer has been reported to improve pancreatitis. In addition, there is no increase in adverse events such as cardiovascular complications such as heart failure with infusions of about 3000-4000 ml/day, and it can be considered that safety is relatively ensured.

Standard treatment (control group): normal infusion group
ERCP has a risk of complications such as bleeding and pancreatitis due to the procedure, and in Japan, it is generally available for fasting and infusion on the day of the endoscope. The general infusion volume is about 1.5 ml/kg/h to 2000 ml/day. In this study, we will examine the group that receives a general infusion volume as the standard treatment group (control group).

About the risks and benefits of study treatment
With regard to benefits, it is expected that the incidence of pancreatitis, the severity of pancreatitis, the number of hospital stays, and the mortality rate will decrease.
With regard to risk, no serious adverse events have been reported from previous reports, but excess fluid may cause heart failure, edema, or pleural and ascites. In addition, the patients assigned to the control group do not undergo the infusion load during ERCP as in the conventional ordinary medical treatment, but from the viewpoint of protecting the subject, if it is diagnosed as pancreatitis by examination during the observation period and blood test (when abdominal pain appears) , At the time of appearance of hyperpancreatic enzymeemia), treatment of pancreatitis including infusion therapy is started immediately (Intention to treat analysis).

(Treatment for clinical research subjects)
Fast food is given 12 hours before ERCP. 3 hours prior to ERCP enforcement
Start the infusion at a maintenance infusion volume of 1.5 ml/kg/h (or 2000 ml/24 h) before the start of ERCP.
Maintenance infusion should be extracellular fluid (Lactated Ringer's solution) or maintenance fluid (No. 3 solution).

For patients in the infusion group, additional infusion of 2 ml/kg/h:8h (or 1000ml/8h) will be started from the beginning of ERCP (supine position).
The content of the infusion solution shall be extracellular fluid (lactated Ringer's solution).
If there is no abdominal symptom, no abnormality on blood test, and no other complications, the meal is restarted the next morning (within 24 hours after ERCP) from ERCP.
The volume of infusion after 24 hours from ERCP (next day) is at the discretion of the attending physician, and post-treatment after the completion of treatment in this study is not limited.

When pancreatitis is diagnosed, a large volume of infusion is required to treat acute pancreatitis, so the volume of infusion should be determined by the attending physician. From the viewpoint of subject protection, if pancreatitis is diagnosed by a medical examination or blood test during the observation period (when abdominal pain appears or when hyperpancreatic enzymeemia appears), promptly administer large volume infusion therapy (eg, 2 ml/kg/h). Start including pancreatitis treatment.

Outcome(s)

Primary Outcome

Post-ERCP pancreatitis incidence: efficacy endpoint
This study examines the post-ERCP pancreatitis preventive effect of fluid loading. Therefore, the primary evaluation item this time is the post-ERCP pancreatitis incidence rate as a direct evaluation item.

Diagnostic criteria for post-ERCP pancreatitis
(1) Newly developed upper abdominal pain
(2) Pancreatic enzymes (amylase and/or lipase) increased more than 3 times the institutional upper limit of normal
(3) (1) and (2) within 24 hours after ERCP
(4) Hospitalization extension of 2 nights or more
Post-ERCP pancreatitis if all of the above are met

Secondary Outcome

1) Severity evaluation by Cotton classificationSeverity endpoint Mild: Clinical symptoms of acute pancreatitis, and amylase at least 3 times normal after 24 hours of procedure, requiring emergency hospitalization, or extended hospitalization for 2-3 days Moderate: Hospitalization for 4-10 days Severe cases requiring: 10 days or more hospitalization, necrosis or pseudocyst formation, or percutaneous drainage or surgery required2-1) Severity evaluation based on pancreatitis clinical practice guidelines Severe pancreatitis Judgment items: Prognostic factors (described below) 3 points or more or contrast CT Grade 2 points or more2-2) Post-ERCP pancreatitis CT Grade (evaluation of pancreatitis severity by CT): Efficacy endpointCT Grade classification by contrast-enhanced CT; Evaluate the extent of inflammation outside the pancreas and the area of poor contrast of the pancreas as follows.3) Severity assessment by Atlanta classification: efficacy endpointFor the following, follow-up including late complications will be performed for at least 30 days after ERCP.
Presence or absence of other complications (pancreatitis after late ERCP, bleeding, renal disorder, heart failure, etc.)Length of hospitalization.
Examination of relevance to other factors (With or without NSAIDs, with or without pancreatic stent placement, with or without history of pancreatitis, with or without ERCP, with or without EST, with or without precut, with or without pancreatography, papillary dysfunction, with nipple resection, with trainees, gender, age, between institutions, etc.)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

(1) Patients aged 20 to 85 at the time of consent acquisition
(2) Gender: Any
(3) Patients who are clinically indicated for ERCP and undergo ERCP (malignant biliary stricture, pancreatic cancer, acute cholangitis, common bile duct stone, IgG4 sclerosing cholangitis, primary sclerosing cholangitis, etc.)
(4) Post-ERCP pancreatitis risk (moderate or higher)
(5) PS is 2 or less
(6) Patients who can take oral drugs, meals and beverages
(7) Patients expected to have stable primary disease (including cancer) 6 months after registration during the observation period
(8) Patients who have written informed consent to participate in this study, who comply with the compliance items during this study participation, who can receive the medical examination prescribed in this study plan and report symptoms etc.

Exclude criteria

(1) Patients with low risk of post-ERCP pancreatitis (confirmed cases of chronic pancreatitis, pancreatic head tumor, periodic biliary stent replacement)
(2) Patients with acute pancreatitis
(3) Patients with hypotension including sepsis
(4) Heart failure patients (NYHA Class II or above)
(5) Patients with renal failure (creatinine clearance <30 mL/min)
(6) Patients with liver failure (patients with cirrhosis and ascites)
(7) Patients with respiratory failure (defined as oxygen saturation <90%)
(8) Hyponatremia (Na+ levels <130mEq/L)
(9) Hypernatremia (Na+ levels> 150mEq/L)
(10) Hypokalemia (K+ levels <3.0mEq/L)
(11) Patients who are pregnant or breastfeeding, patients who wish to become pregnant during the study period, patients who wish to become pregnant of a partner during the study period.
(12) In addition, patients who are judged to be unsuitable for study participation by the investigator or investigator based on combination therapy and medical findings.
(13) Patients in other clinical studies or clinical trials

Related Information

• Primary Sponsor: Kurita Yusuke