Pancreatitis
Conditions
Keywords
Extracorporeal Shock Wave lithotripsy(ESWL), Prophylaxis, Indomethacin, Chronic pancreatitis
Brief summary
The purpose of the study is to determine whether rectal indomethacin reduces the incidence of post-ESWL pancreatitis.
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.
Interventions
100mg rectal indomethacin 30min before ESWL
30min before ESWL
Sponsors
Changhai Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indomethacin Subjects will be randomized to receive a 100-mg indomethacin suppository 30 min before ESWL.
indomethacin suppository: 100mg rectal indomethacin 30min before ESWL | 685 |
| Glycerin Subjects will be randomized to receive either a 100-mg identical-appearing placebo (glycerin suppository) 30 min before ESWL.
Glycerin Suppository: 30min before ESWL | 685 |
| Total | 1,370 |
Baseline characteristics
| Characteristic | Glycerin | Total | Indomethacin |
|---|---|---|---|
| Age, Continuous | 45.84 years STANDARD_DEVIATION 12.43 | 45.35 years STANDARD_DEVIATION 12.38 | 44.85 years STANDARD_DEVIATION 12.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 685 Participants | 1370 Participants | 685 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 197 Participants | 391 Participants | 194 Participants |
| Sex: Female, Male Male | 488 Participants | 979 Participants | 491 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 685 | 0 / 685 |
| other Total, other adverse events | 0 / 685 | 0 / 685 |
| serious Total, serious adverse events | 0 / 685 | 0 / 685 |
Outcome results
Primary
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.
Time frame: up to 1 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Indomethacin | the Incidence of Post-ESWL Pancreatitis | 60 Participants |
| Glycerin | the Incidence of Post-ESWL Pancreatitis | 84 Participants |
Secondary
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.
Time frame: up to 1 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Asymptomatic Hyperamylasemia | 189 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Hematuria | 18 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Steinstrasse | 0 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Hematemesis | 9 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Infection | 5 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Melena | 19 Participants |
| Indomethacin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Perforation | 0 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Melena | 16 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Asymptomatic Hyperamylasemia | 197 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Infection | 13 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Steinstrasse | 1 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Hematuria | 25 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Hematemesis | 14 Participants |
| Glycerin | the Incidence and Severity of Asymptomatic Hyperamylasemia and Other Post-ESWL Complications | Perforation | 1 Participants |
Secondary
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.
Time frame: up to 1 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Indomethacin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Mild | 59 Participants |
| Indomethacin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Moderate | 1 Participants |
| Indomethacin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Severe | 0 Participants |
| Glycerin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Moderate | 5 Participants |
| Glycerin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Severe | 0 Participants |
| Glycerin | the Severity of Post-ESWL Pancreatitis Measured as Consensus Definitions for the Major Complications of ERCP（Endoscopic Retrograde Cholangiopancreatography ） | Mild | 79 Participants |
Other Pre-specified
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.
Time frame: up to 1 months