Rectal Indomethacin to Prevent Post ESWL-pancreatitis (RIPEP)

Rectally Administered Indomethacin to Prevent Post-ESWL-pancreatitis (RIPEP)

The purpose of the study is to determine whether rectal indomethacin reduces the incidence of post-ESWL pancreatitis.

Study Overview

• Status: Completed
• Conditions: Pancreatitis
• Intervention / Treatment: Drug: indomethacin suppository; Drug: Glycerin Suppository

Detailed Description

It is a prospective, double-blind, randomized controlled trial. Patients with painful chronic pancreatitis and pancreatic stones (> 5 mm in diameter) who are treated with ESWL at Changhai Hospital will be randomly allocated to indomethacin or placebo therapy before the procedure.

• Study Type: Interventional
• Enrollment (Actual): 1370
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• any patient with chronic pancreatitis and pancreatic stones (> 5 mm in diameter) undergoing P-ESWL
• at least 18 years old
• provides informed consent

Exclusion Criteria:

• readmitted to the hospital during the enrollment of the study
• contraindications to ESWL
• suspected or established malignancy
• pancreatic ascites
• receiving NSAIDs within 7 days
• contraindication to NSAIDs (including gastrointestinal hemorrhage within 4 weeks or renal dysfunction with serum creatinine >120 μmol/L)
• presence of coagulopathy or received anticoagulation therapy within 3 days
• acute pancreatitis within 3 days
• known active cardiovascular or cerebrovascular disease
• pregnant or breastfeeding women
• without a rectum (ie, status post-total proctocolectomy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indomethacin; Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL.	Drug: indomethacin suppository; 100mg rectal indomethacin 30min before ESWL
Placebo Comparator: Glycerin; Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL.	Drug: Glycerin Suppository; 30min before ESWL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Incidence of Post-ESWL Pancreatitis	Patients were identified as post-ESWL pancreatitis if meeting two out of three criteria: pain consistent with acute pancreatitis; amylase or lipase>3 times normal limit; characteristic findings on imaging, in according to the Revised Atlanta International consensus.	up to 1 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications	Asymptomatic hyperamylasemia was defined as an increase in serum amylase compared with pre-ESWL levels and beyond the upper limit of the normal range but showing no related symptoms. Serum amylase will be measured in all study patients at 3 and 24 hours after the procedure and subsequently at clinical discretion. Other post-ESWL complications including bleeding, infection, steinstrasse and perforation. Bleeding is related to clinical evidence，the level of hemoglobin ( measured at 24 hours after the procedure and at clinical discretion) and treatments. Infection is related to temperature and treatment. Steinstrasse is related to abdominal pain degree and the combination of other complications. Perforation is related to treatment.	up to 1 months
the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ）	Post-ESWL complications are also stratified as mild, moderate and severe depending mainly on the length of hospitalization and the need for invasive treatment.	up to 1 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Risks in the Subgroup of Potential Risk Factors for Post -ESWL Pancreatitis Will be Assessed by SPSS（Statistical Product and Service Solutions，a Statistical Software）.	Potential risk factors including sex, steatorrhea, pancreas divisum, frequent attack of acute pancreatitis (≥ 1/year), diabetes, CBD（common bile duct） stenosis, alcohol consumption, multiple stones, position (the 30°-right supine position) and shock wave frequency ≥100/min.These will be assess to determine whether the treatment effect differ in these pre-specified factors.	up to 1 months

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Zhuan Liao, MD, Changhai Hospital

Publications and helpful links

General Publications

• Qian YY, Ru N, Chen H, Zou WB, Wu H, Pan J, Li B, Xin L, Guo JY, Tang XY, Hu LH, Jin ZD, Wang D, Du YQ, Wang LW, Li ZS, Liao Z. Rectal indometacin to prevent pancreatitis after extracorporeal shock wave lithotripsy (RIPEP): a single-centre, double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):238-244. doi: 10.1016/S2468-1253(21)00434-9. Epub 2022 Jan 25.
• Qian YY, Chen H, Tang XY, Jiang X, Qian W, Zou WB, Xin L, Li B, Qi YF, Hu LH, Zou DW, Jin ZD, Wang D, Du YQ, Wang LW, Liu F, Li ZS, Liao Z. Rectally administered indomethacin to prevent post-ESWL-pancreatitis (RIPEP): study protocol for a randomized controlled trial. Trials. 2017 Nov 2;18(1):513. doi: 10.1186/s13063-017-2250-7.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: May 29, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (Estimate): June 13, 2016

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Prophylaxis; Chronic pancreatitis; Indomethacin; Extracorporeal Shock Wave lithotripsy(ESWL)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Protective Agents; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Cryoprotective Agents; Indomethacin; Glycerol
• Other Study ID Numbers: ESWL-pancreatitis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No