RIPEP: Rectal Indomethacin to Prevent Post ESWL-pancreatitis

• Sponsor: Changhai Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02797067
• Collaborator: (none)
• Enrollment: 1,370
• Location: 1
• Arms: 2
• Actual Duration (Months): 62
• Patients Per Site Per Month: 22.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pancreatitis	Drug: indomethacin suppository; Drug: Glycerin Suppository	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 1370 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Rectally Administered Indomethacin to Prevent Post-ESWL-pancreatitis (RIPEP)
• Actual Study Start Date: May 31, 2016
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Aug 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. the Incidence of Post-ESWL Pancreatitis [up to 1 months]

   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.

Secondary Outcome Measures

1. the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications [up to 1 months]

   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.

2. the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） [up to 1 months]

   Post-ESWL complications are also stratified as mild, moderate and severe depending mainly on the length of hospitalization and the need for invasive treatment.

Other Outcome Measures

1. 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）. [up to 1 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shanghai Changhai Hospital	Shanghai		China

Sponsors and Collaborators

• Changhai Hospital

Investigators

• Principal Investigator: Zhuan Liao, MD, Changhai Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 20, 2017

More Information

Publications

None provided.

• Responsible Party: Zhuan Liao, Professor, Changhai Hospital
• ClinicalTrials.gov Identifier: NCT02797067
• Other Study ID Numbers: ESWL-pancreatitis
• First Posted: Jun 13, 2016
• Last Update Posted: May 26, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zhuan Liao, Professor, Changhai Hospital: Extracorporeal Shock Wave lithotripsy(ESWL); Prophylaxis; Indomethacin; Chronic pancreatitis
• Additional relevant MeSH terms: Pancreatitis; Indomethacin; Glycerol

Study Results

Participant Flow

Arm/Group Title	Indomethacin	Glycerin
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL	Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL
Period Title: Overall Study
STARTED	685	685
COMPLETED	685	685
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Indomethacin	Glycerin	Total
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL	Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL	Total of all reporting groups
Overall Participants	685	685	1370
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.85 (12.32)	45.84 (12.43)	45.35 (12.38)
Sex: Female, Male (Count of Participants)
Female	194 28.3%	197 28.8%	391 28.5%
Male	491 71.7%	488 71.2%	979 71.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	685 100%	685 100%	1370 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	the Incidence of Post-ESWL Pancreatitis
Description	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.
Time Frame	up to 1 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Glycerin
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL	Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL
Measure Participants	685	685
Count of Participants [Participants]	60 8.8%	84 12.3%

2. Secondary Outcome

Title	the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications
Description	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.
Time Frame	up to 1 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Glycerin
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL	Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL
Measure Participants	685	685
Infection	5 0.7%	13 1.9%
Steinstrasse	0 0%	1 0.1%
Perforation	0 0%	1 0.1%
Asymptomatic Hyperamylasemia	189 27.6%	197 28.8%
Hematuria	18 2.6%	25 3.6%
Hematemesis	9 1.3%	14 2%
Melena	19 2.8%	16 2.3%

3. Secondary Outcome

Title	the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ）
Description	Post-ESWL complications are also stratified as mild, moderate and severe depending mainly on the length of hospitalization and the need for invasive treatment.
Time Frame	up to 1 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indomethacin	Glycerin
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL	Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL
Measure Participants	685	685
Mild	59 8.6%	79 11.5%
Moderate	1 0.1%	5 0.7%
Severe	0 0%	0 0%

4. Other Pre-specified Outcome

Title	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）.
Description	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.
Time Frame	up to 1 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From administration of rectal indomethacin/glycerin suppositories to charge from hospital, up to one month
Arm/Group Title	Indomethacin		Glycerin
Arm/Group Description	Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL. indomethacin suppository: 100mg rectal indomethacin 30min before ESWL		Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL. Glycerin Suppository: 30min before ESWL
All Cause Mortality
	Indomethacin		Glycerin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/685 (0%)		0/685 (0%)
Serious Adverse Events
	Indomethacin		Glycerin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/685 (0%)		0/685 (0%)
Other (Not Including Serious) Adverse Events
	Indomethacin		Glycerin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/685 (0%)		0/685 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.