<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01717599</url>
  </required_header>
  <id_info>
    <org_study_id>4-2012-0466</org_study_id>
    <nct_id>NCT01717599</nct_id>
  </id_info>
  <brief_title>Intramuscular Diclofenac in the Prevention of Post-ERCP Pancreatitis</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pancreatitis is one of the major complications of ERCP. It has been shown that NSAIDs are&#xD;
      potent inhibitors of phospholipase A2, activity which is increased in pancreatitis. The only&#xD;
      one study with IM diclofenac showed reduction of post-ERCP pancreatitis without SOD&#xD;
      (sphincter of Oddi dysfunction) by subgroup analysis in small study population. Therefore the&#xD;
      investigators must need large scaled randomized control study including of SOD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study described in this report will be approved by the ethics committee of Yonsei&#xD;
      University School of Medicine, Seoul, Korea. Between July 2012 and February 2013, 380&#xD;
      patients fulfilled the inclusion criteria, 380 of whom were included in the final analysis.&#xD;
      Consecutive patients were recruited for the study who presented to the Yonsei University&#xD;
      Medical Center with variable symptom or cause for ERCP older than 20years. Patients were&#xD;
      excluded from study participation if they had a contraindication for diclofenac, including&#xD;
      patients with recently diagnosed peptic ulcer disease or active/recent gastrointestinal&#xD;
      hemorrhage within 4 weeks, renal failure(Cr &gt; 1.4), those who had taken an NSAID during the&#xD;
      preceding week(ASA 325 mg daily or less acceptable), those who developed acute pancreatitis&#xD;
      during the 2 weeks before ERCP, those with a history of chronic calcific pancreatitis or&#xD;
      allergy to aspirin or NSAID, and those who did not agree to participate in the study.&#xD;
      Additionally, if state of patients was intrauterine pregnancy or breast feeding mother, they&#xD;
      were excluded. Entry to the study was restricted to patients advised to have endoscopic&#xD;
      retrograde cholangiography with or without pancreatography for extrahepatic cholestasis&#xD;
      and/or impaired liver function tests.&#xD;
&#xD;
      The patients received 90 mg IM diclofenac available in our hospital immediately after ERCP at&#xD;
      recovery room. Patients were observed in the recovery room for at least 90 minutes after the&#xD;
      procedure. Patients in whom abdominal pain developed during this observation period were&#xD;
      admitted to the hospital (or for current inpatients, kept in the hospital). Decisions&#xD;
      regarding evaluation of complications after the procedure and in-hospital care were left to&#xD;
      the discretion of the endoscopist and clinical-service staff members, who were unaware of&#xD;
      study-group assignments.&#xD;
&#xD;
      Patients who were discharged after an uneventful ERCP were contacted by telephone within 5&#xD;
      days to capture delayed occurrence of the primary end point. Patient demographics, risk&#xD;
      factors, ERCP procedural elements, and follow-up data were recorded on standardized&#xD;
      data-collection forms by an investigator or coordinator who was unaware of study-group&#xD;
      assignments. The intramuscular route was selected on the basis of available small sized data&#xD;
      suggesting that intramuscular NSAIDs are effective in preventing post-ERCP pancreatitis,&#xD;
      perhaps owing to more rapid and complete bioavailability than with oral administration. (1)&#xD;
      At the end of each procedure, the researchers recorded the details of the maneuvers&#xD;
      performed, including the total time of the procedure, the number of attempts at cannulation,&#xD;
      the number of pancreatic duct cannulations, the final diagnosis, and whether a&#xD;
      sphincterotomy, a needle-knife papillotomy, or stent placement were performed. We did not use&#xD;
      pancreatic duct stenting for prevention of pancreatitis. Patients were sedated with IV&#xD;
      midazolam and IV continuous infusion of propofol under monitoring by anesthesiologist during&#xD;
      whole time of procedure. Xylocaine spray was used as a local anesthetic. Serum amylase was&#xD;
      determined 4 hours after ERCP.&#xD;
&#xD;
      If the 4-hours serum amylase level was &lt; 3 times the upper normal limit and there was no&#xD;
      clinical evidence of acute pancreatitis at that time, patients were allowed free oral fluids&#xD;
      and a diet. If the 4- hours serum amylase level was &gt; 3 times the upper normal limit and the&#xD;
      patient exhibited pain or nausea and vomiting, then the patient was kept fasting and IV&#xD;
      crystalloid fluids with opiate analgesics were prescribed. The following 24 hours blood tests&#xD;
      were repeated for serum amylase and the patients were interviewed and examined for clinical&#xD;
      evidence of acute pancreatitis.&#xD;
&#xD;
      Acute pancreatitis was defined as serum amylase at least three times the upper limit of&#xD;
      normal range 24hours after the procedure associated with new or increased upper abdomen or&#xD;
      epigastric pain, back pain, and epigastric tenderness and hospitalization or prolongation of&#xD;
      existing hospitalization for at least 2 nights. Patients with persistent signs and symptoms&#xD;
      of pancreatitis after 48 hours underwent contrast-enhanced computed tomography.&#xD;
&#xD;
      Pancreatitis was graded as mild, moderate, or severe. The severity was determined according&#xD;
      to consensus guidelines, with mild post-ERCP pancreatitis resulting in a hospitalization of&#xD;
      ≤3 days, moderate post-ERCP pancreatitis resulting in a hospitalization of 4-10 days, and&#xD;
      severe post-ERCP pancreatitis resulting in a hospitalization of &gt; 10 days, or leading to the&#xD;
      development of pancreatic necrosis or pseudocyst, or requiring percutaneous or surgical&#xD;
      intervention.&#xD;
&#xD;
      Sphincter of Oddi dysfunction (SOD) was defined according following Classification. Biliary&#xD;
      type I SOD was defined as biliary-type abdominal pain, liver enzyme elevation, and common&#xD;
      bile duct dilation &gt; 9mm. Biliary type II SOD was defined as biliary-type abdominal pain and&#xD;
      either abnormal liver enzymes or a dilated bile duct. Biliary type III SOD was defined as&#xD;
      biliary-type pain without any other objective findings. Pancreatic type I SOD was defined as&#xD;
      pancreatic-type pain and a dilated pancreatic duct and elevated pancreatic enzymes, or&#xD;
      recurrent acute pancreatitis. Type II pancreatic SOD was defined as pancreatic-type pain and&#xD;
      a dilated pancreatic duct or elevated pancreatic enzymes. Type III pancreatic SOD was defined&#xD;
      as pancreatic-type pain alone.&#xD;
&#xD;
      The instruments used were cannula, sphincterotome, guidewire, and stone basket (Olympus,&#xD;
      Japan).&#xD;
&#xD;
      Adverse events were defined as reported previously. Any cases of post-ERCP pancreatitis,&#xD;
      other complications of the procedure, and adverse events that were potentially attributable&#xD;
      to the study drug were reported to the local institutional review board and the data and&#xD;
      safety monitoring board. These reportable adverse events were gastrointestinal bleeding,&#xD;
      perforation, infection, renal failure, allergic reaction, myocardial infarction,&#xD;
      cerebrovascular accident, and death.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 29, 2012</start_date>
  <completion_date type="Actual">August 28, 2013</completion_date>
  <primary_completion_date type="Actual">August 28, 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of post ERCP pancreatitis</measure>
    <time_frame>24hours after the procedure(ERCP)</time_frame>
    <description>Acute pancreatitis was defined as serum amylase at least three times the upper limit of normal range 24hours after the procedure associated with new or increased upper abdomen or epigastric pain, back pain, and epigastric tenderness and hospitalization or prolongation of existing hospitalization for at least 2 nights.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">343</enrollment>
  <condition>Post ERCP Pancreatitis</condition>
  <arm_group>
    <arm_group_label>Diclofenac group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo(normal saline) group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diclofenac</intervention_name>
    <description>Diclofenac 90mg, 2ml/A, IM(intramuscular) injection immediately after procedure of ERCP</description>
    <arm_group_label>Diclofenac group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>normal saline</intervention_name>
    <description>normal saline 2ml/A, IM(intramuscular) injection immediately after procedure of ERCP</description>
    <arm_group_label>Placebo(normal saline) group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Consecutive patients were recruited for the study who presented to the Yonsei University&#xD;
        Medical Center with variable symptom or cause for ERCP older than 20 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients were excluded from study participation if:&#xD;
&#xD;
          -  they had a contraindication for diclofenac,&#xD;
&#xD;
          -  including patients with recently diagnosed peptic ulcer disease or active/recent&#xD;
             gastrointestinal hemorrhage within 4 weeks,&#xD;
&#xD;
          -  renal failure (Cr &gt; 1.4),&#xD;
&#xD;
          -  those who had taken an NSAID during the preceding week (ASA 325 mg daily or less&#xD;
             acceptable),&#xD;
&#xD;
          -  those who developed acute pancreatitis during the 2 weeks before ERCP,&#xD;
&#xD;
          -  those with a history of chronic calcific pancreatitis or allergy to aspirin or NSAID,&#xD;
             and&#xD;
&#xD;
          -  those who did not agree intramuscular injection. Additionally, if state of patients&#xD;
             was intrauterine pregnancy or breast feeding mother, they were excluded. Finally,&#xD;
             patients were excluded for study if they had bleeding tendency and contraindication&#xD;
             for intramuscular injection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>May 3, 2021</last_update_submitted>
  <last_update_submitted_qc>May 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Post ERCP pancreatitis</keyword>
  <keyword>Diclofenac</keyword>
  <keyword>NSAID</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diclofenac</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01717599
org study id: 4-2012-0466
nct id: NCT01717599
lead sponsor: 
has dmc: No
Pancreatitis is one of the major complications of ERCP. It has been shown that NSAIDs are
      potent inhibitors of phospholipase A2, activity which is increased in pancreatitis. The only
      one study with IM diclofenac showed reduction of post-ERCP pancreatitis without SOD
      (sphincter of Oddi dysfunction) by subgroup analysis in small study population. Therefore the
      investigators must need large scaled randomized control study including of SOD.
The study described in this report will be approved by the ethics committee of Yonsei
      University School of Medicine, Seoul, Korea. Between July 2012 and February 2013, 380
      patients fulfilled the inclusion criteria, 380 of whom were included in the final analysis.
      Consecutive patients were recruited for the study who presented to the Yonsei University
      Medical Center with variable symptom or cause for ERCP older than 20years. Patients were
      excluded from study participation if they had a contraindication for diclofenac, including
      patients with recently diagnosed peptic ulcer disease or active/recent gastrointestinal
      hemorrhage within 4 weeks, renal failure(Cr > 1.4), those who had taken an NSAID during the
      preceding week(ASA 325 mg daily or less acceptable), those who developed acute pancreatitis
      during the 2 weeks before ERCP, those with a history of chronic calcific pancreatitis or
      allergy to aspirin or NSAID, and those who did not agree to participate in the study.
      Additionally, if state of patients was intrauterine pregnancy or breast feeding mother, they
      were excluded. Entry to the study was restricted to patients advised to have endoscopic
      retrograde cholangiography with or without pancreatography for extrahepatic cholestasis
      and/or impaired liver function tests.

      The patients received 90 mg IM diclofenac available in our hospital immediately after ERCP at
      recovery room. Patients were observed in the recovery room for at least 90 minutes after the
      procedure. Patients in whom abdominal pain developed during this observation period were
      admitted to the hospital (or for current inpatients, kept in the hospital). Decisions
      regarding evaluation of complications after the procedure and in-hospital care were left to
      the discretion of the endoscopist and clinical-service staff members, who were unaware of
      study-group assignments.

      Patients who were discharged after an uneventful ERCP were contacted by telephone within 5
      days to capture delayed occurrence of the primary end point. Patient demographics, risk
      factors, ERCP procedural elements, and follow-up data were recorded on standardized
      data-collection forms by an investigator or coordinator who was unaware of study-group
      assignments. The intramuscular route was selected on the basis of available small sized data
      suggesting that intramuscular NSAIDs are effective in preventing post-ERCP pancreatitis,
      perhaps owing to more rapid and complete bioavailability than with oral administration. (1)
      At the end of each procedure, the researchers recorded the details of the maneuvers
      performed, including the total time of the procedure, the number of attempts at cannulation,
      the number of pancreatic duct cannulations, the final diagnosis, and whether a
      sphincterotomy, a needle-knife papillotomy, or stent placement were performed. We did not use
      pancreatic duct stenting for prevention of pancreatitis. Patients were sedated with IV
      midazolam and IV continuous infusion of propofol under monitoring by anesthesiologist during
      whole time of procedure. Xylocaine spray was used as a local anesthetic. Serum amylase was
      determined 4 hours after ERCP.

      If the 4-hours serum amylase level was < 3 times the upper normal limit and there was no
      clinical evidence of acute pancreatitis at that time, patients were allowed free oral fluids
      and a diet. If the 4- hours serum amylase level was > 3 times the upper normal limit and the
      patient exhibited pain or nausea and vomiting, then the patient was kept fasting and IV
      crystalloid fluids with opiate analgesics were prescribed. The following 24 hours blood tests
      were repeated for serum amylase and the patients were interviewed and examined for clinical
      evidence of acute pancreatitis.

      Acute pancreatitis was defined as serum amylase at least three times the upper limit of
      normal range 24hours after the procedure associated with new or increased upper abdomen or
      epigastric pain, back pain, and epigastric tenderness and hospitalization or prolongation of
      existing hospitalization for at least 2 nights. Patients with persistent signs and symptoms
      of pancreatitis after 48 hours underwent contrast-enhanced computed tomography.

      Pancreatitis was graded as mild, moderate, or severe. The severity was determined according
      to consensus guidelines, with mild post-ERCP pancreatitis resulting in a hospitalization of
      ≤3 days, moderate post-ERCP pancreatitis resulting in a hospitalization of 4-10 days, and
      severe post-ERCP pancreatitis resulting in a hospitalization of > 10 days, or leading to the
      development of pancreatic necrosis or pseudocyst, or requiring percutaneous or surgical
      intervention.

      Sphincter of Oddi dysfunction (SOD) was defined according following Classification. Biliary
      type I SOD was defined as biliary-type abdominal pain, liver enzyme elevation, and common
      bile duct dilation > 9mm. Biliary type II SOD was defined as biliary-type abdominal pain and
      either abnormal liver enzymes or a dilated bile duct. Biliary type III SOD was defined as
      biliary-type pain without any other objective findings. Pancreatic type I SOD was defined as
      pancreatic-type pain and a dilated pancreatic duct and elevated pancreatic enzymes, or
      recurrent acute pancreatitis. Type II pancreatic SOD was defined as pancreatic-type pain and
      a dilated pancreatic duct or elevated pancreatic enzymes. Type III pancreatic SOD was defined
      as pancreatic-type pain alone.

      The instruments used were cannula, sphincterotome, guidewire, and stone basket (Olympus,
      Japan).

      Adverse events were defined as reported previously. Any cases of post-ERCP pancreatitis,
      other complications of the procedure, and adverse events that were potentially attributable
      to the study drug were reported to the local institutional review board and the data and
      safety monitoring board. These reportable adverse events were gastrointestinal bleeding,
      perforation, infection, renal failure, allergic reaction, myocardial infarction,
      cerebrovascular accident, and death.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Incidence of post ERCP pancreatitis
time frame: 24hours after the procedure(ERCP)
description: Acute pancreatitis was defined as serum amylase at least three times the upper limit of normal range 24hours after the procedure associated with new or increased upper abdomen or epigastric pain, back pain, and epigastric tenderness and hospitalization or prolongation of existing hospitalization for at least 2 nights.
arm group label: Diclofenac group
arm group type: Experimental
arm group label: Placebo(normal saline) group
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Diclofenac
description: Diclofenac 90mg, 2ml/A, IM(intramuscular) injection immediately after procedure of ERCP
arm group label: Diclofenac group
intervention type: Drug
intervention name: normal saline
description: normal saline 2ml/A, IM(intramuscular) injection immediately after procedure of ERCP
arm group label: Placebo(normal saline) group
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Pancreatitis
mesh term: Diclofenac