<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/NCT03814421</url>
  </required_header>
  <id_info>
    <org_study_id>2016-SCMC-008-00</org_study_id>
    <nct_id>NCT03814421</nct_id>
  </id_info>
  <brief_title>Efficacy of Low Dose Intravenous Proton Pump Inhibitor for Peptic Ulcer Bleeding</brief_title>
  <official_title>Effect of Intermittent Versus Continuous Intravenous Pantoprazole for Prevention of Bleeding After Endoscopic Therapy of Bleeding Peptic Ulcers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Changwon Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samsung Changwon Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      We prepare this study to compare the efficacy of intermittent intravenous PPI infusion&#xD;
      (relatively low dose PPI therapy) than continous PPI infusion method. Our hypothesis is that&#xD;
      intermittent (40mg as a bolus injection daily for 72 hours) PPI therapy is not inferior to&#xD;
      conventional high dose therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Current guidelines recommend an intravenous bolus dose of a proton pump&#xD;
      inhibitor(PPI) followed by continuous PPI infusion after endoscopic therapy in patients with&#xD;
      high-risk peptic ulcer bleeding. However, intermittent PPI have not been inferior to&#xD;
      continuous PPI infusion regimens in recent studies.&#xD;
&#xD;
      Objective The aim of this study was to compare the effect of intermittent (40mg as a bolus&#xD;
      injection daily for 72hours) versus continuous (40mg as a bolus injection followed by&#xD;
      continuous infusion at 8mg/hr for 72hours) intravenous pantoprazole for prevention of&#xD;
      bleeding after endoscopic therapy of peptic ulcer bleeding. Also, the same comparison was&#xD;
      performed in high-risk patients (Rockall scores ≥6).&#xD;
&#xD;
      Methods This single center cross-sectional study was conducted from january 2010 through&#xD;
      december 2013. Patients who presented with overt or suspected upper gastrointestinal bleeding&#xD;
      based on hematemesis and/or melena were eligible. These eligible patients were required to&#xD;
      have a peptic ulcer with bleeding on emergency endoscopy performed within 24 hours after&#xD;
      hospitalization. Exclusion criteria were refusal of endoscopy, gastrointestinal malignancy,&#xD;
      Mallory-Weiss syndrome, variceal bleeding, bleeding d/t endoscopic procedure, small bowel&#xD;
      bleeding, serious medical disease, etc. Demographic and medical data were obtained from the&#xD;
      patients' medical records. Current or past history of medical diagnosis and drug history were&#xD;
      also recorded. Statistical analysis performed using SPSS 21.0 software.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 15, 2016</start_date>
  <completion_date type="Anticipated">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>rebleeding rates within 7 days</measure>
    <time_frame>Within 7 days from enrollment of patient</time_frame>
    <description>Rebleeding was defined that endoscopy confirms that the bleeding is completely controlled and the following outcomes occur after initial vital signs are stabilized.&#xD;
when a new hematemesis, hematochezia, occurs.&#xD;
melena occurs and blood pressure decreases (less than 90 mmHg) or pulse rate increase (110 beats per minute) or hemoglobin decline (greater than 3 g / dL) within 24 hours.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Transfusion requirement</measure>
    <time_frame>within 7 days from enrollment of patient</time_frame>
    <description>The amount of transfusion that occurred during the period when the patient was in hospital was recorded as unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital stay</measure>
    <time_frame>within 1 years from enrollment of patient</time_frame>
    <description>length of hospital stay - From the day the patient visits the emergency room to the day when the patient gets discharged</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death related with Upper GI bleeding</measure>
    <time_frame>within 1 years from enrollment of patient</time_frame>
    <description>All-cause or bleeding-related mortality was observed within 1 year of patient enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Operation d/t Upper GI bleeding</measure>
    <time_frame>within 1 years from enrollment of patient</time_frame>
    <description>This result is defined as exploratory laparatomy associated with peptic ulcer bleeding, gastric and duodenal resection anastomosis, and vagotomy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Peptic Ulcer Hemorrhage</condition>
  <condition>Peptic Ulcer, Acute With Hemorrhage</condition>
  <condition>Peptic Ulcer</condition>
  <condition>Proton Pump Inhibitor Overdose</condition>
  <arm_group>
    <arm_group_label>Low dose intermittent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pantoprazole 40mg as a bolus injection daily for 72hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose continous</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pantoprazole 40mg as a bolus injection followed by continuous infusion at 8mg/hr for 72hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>intermittent (40mg as a bolus injection daily for 72hours)</intervention_name>
    <description>Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor(PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding peptic ulcers. However, recent many studies suggests intermittent low dose PPI infusion might have equal efficacy at preventing peptic ulcer hemorrhage recurrence. So, the present investigator assumed that intermittent administration of proton pump inhibitor will not be different from administration of continuous proton pump inhibitor for the prevention of rebleeding in patients with peptic ulcer bleeding. Also, intermittent proton pump inhibitor administration in patients with high risk of rebleeding (Rockall score 6 points or more) will not be different from prevention of rebleeding compared with continuous proton pump inhibitor administration.</description>
    <arm_group_label>High dose continous</arm_group_label>
    <arm_group_label>Low dose intermittent</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18 years or older who had undergone gastroscopy for melena, hematochezia&#xD;
             or hematemesis due to bleeding peptic ulcers were eligible. These eligible patients&#xD;
             were required to have a peptic ulcer with bleeding on emergency endoscopy performed&#xD;
             within 24 hours after hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  refusal of endoscopy, gastrointestinal malignancy, Mallory-Weiss syndrome, variceal&#xD;
             bleeding, bleeding d/t endoscopic procedure, small bowel bleeding, serious medical&#xD;
             disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Samsung Changwon Hospital</name>
      <address>
        <city>Changwon</city>
        <state>Gyeongsangnam-do</state>
        <zip>51353</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Sung JJ, Chiu PW, Chan FKL, Lau JY, Goh KL, Ho LH, Jung HY, Sollano JD, Gotoda T, Reddy N, Singh R, Sugano K, Wu KC, Wu CY, Bjorkman DJ, Jensen DM, Kuipers EJ, Lanas A. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018. Gut. 2018 Oct;67(10):1757-1768. doi: 10.1136/gutjnl-2018-316276. Epub 2018 Apr 24. Erratum In: Gut. 2019 Feb;68(2):380.</citation>
    <PMID>29691276</PMID>
  </reference>
  <results_reference>
    <citation>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7;2010(7):CD005415. doi: 10.1002/14651858.CD005415.pub3.</citation>
    <PMID>20614440</PMID>
  </results_reference>
  <results_reference>
    <citation>Cook D, Guyatt G. Prophylaxis against Upper Gastrointestinal Bleeding in Hospitalized Patients. N Engl J Med. 2018 Jun 28;378(26):2506-2516. doi: 10.1056/NEJMra1605507. No abstract available.</citation>
    <PMID>29949497</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Samsung Changwon Hospital</investigator_affiliation>
    <investigator_full_name>Jung Won Lee</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peptic Ulcer</mesh_term>
    <mesh_term>Peptic Ulcer Hemorrhage</mesh_term>
    <mesh_term>Ulcer</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_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/NCT03814421
org study id: 2016-SCMC-008-00
nct id: NCT03814421
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
We prepare this study to compare the efficacy of intermittent intravenous PPI infusion
      (relatively low dose PPI therapy) than continous PPI infusion method. Our hypothesis is that
      intermittent (40mg as a bolus injection daily for 72 hours) PPI therapy is not inferior to
      conventional high dose therapy.
Background Current guidelines recommend an intravenous bolus dose of a proton pump
      inhibitor(PPI) followed by continuous PPI infusion after endoscopic therapy in patients with
      high-risk peptic ulcer bleeding. However, intermittent PPI have not been inferior to
      continuous PPI infusion regimens in recent studies.

      Objective The aim of this study was to compare the effect of intermittent (40mg as a bolus
      injection daily for 72hours) versus continuous (40mg as a bolus injection followed by
      continuous infusion at 8mg/hr for 72hours) intravenous pantoprazole for prevention of
      bleeding after endoscopic therapy of peptic ulcer bleeding. Also, the same comparison was
      performed in high-risk patients (Rockall scores ≥6).

      Methods This single center cross-sectional study was conducted from january 2010 through
      december 2013. Patients who presented with overt or suspected upper gastrointestinal bleeding
      based on hematemesis and/or melena were eligible. These eligible patients were required to
      have a peptic ulcer with bleeding on emergency endoscopy performed within 24 hours after
      hospitalization. Exclusion criteria were refusal of endoscopy, gastrointestinal malignancy,
      Mallory-Weiss syndrome, variceal bleeding, bleeding d/t endoscopic procedure, small bowel
      bleeding, serious medical disease, etc. Demographic and medical data were obtained from the
      patients' medical records. Current or past history of medical diagnosis and drug history were
      also recorded. Statistical analysis performed using SPSS 21.0 software.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: rebleeding rates within 7 days
time frame: Within 7 days from enrollment of patient
description: Rebleeding was defined that endoscopy confirms that the bleeding is completely controlled and the following outcomes occur after initial vital signs are stabilized.
when a new hematemesis, hematochezia, occurs.
melena occurs and blood pressure decreases (less than 90 mmHg) or pulse rate increase (110 beats per minute) or hemoglobin decline (greater than 3 g / dL) within 24 hours.
measure: Transfusion requirement
time frame: within 7 days from enrollment of patient
description: The amount of transfusion that occurred during the period when the patient was in hospital was recorded as unit.
measure: Hospital stay
time frame: within 1 years from enrollment of patient
description: length of hospital stay - From the day the patient visits the emergency room to the day when the patient gets discharged
measure: Death related with Upper GI bleeding
time frame: within 1 years from enrollment of patient
description: All-cause or bleeding-related mortality was observed within 1 year of patient enrollment.
measure: Operation d/t Upper GI bleeding
time frame: within 1 years from enrollment of patient
description: This result is defined as exploratory laparatomy associated with peptic ulcer bleeding, gastric and duodenal resection anastomosis, and vagotomy.
arm group label: Low dose intermittent
arm group type: Experimental
description: Pantoprazole 40mg as a bolus injection daily for 72hours
arm group label: High dose continous
arm group type: Active Comparator
description: Pantoprazole 40mg as a bolus injection followed by continuous infusion at 8mg/hr for 72hours
intervention type: Drug
intervention name: intermittent (40mg as a bolus injection daily for 72hours)
description: Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor(PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding peptic ulcers. However, recent many studies suggests intermittent low dose PPI infusion might have equal efficacy at preventing peptic ulcer hemorrhage recurrence. So, the present investigator assumed that intermittent administration of proton pump inhibitor will not be different from administration of continuous proton pump inhibitor for the prevention of rebleeding in patients with peptic ulcer bleeding. Also, intermittent proton pump inhibitor administration in patients with high risk of rebleeding (Rockall score 6 points or more) will not be different from prevention of rebleeding compared with continuous proton pump inhibitor administration.
arm group label: High dose continous
arm group label: Low dose intermittent
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
citation: Sung JJ, Chiu PW, Chan FKL, Lau JY, Goh KL, Ho LH, Jung HY, Sollano JD, Gotoda T, Reddy N, Singh R, Sugano K, Wu KC, Wu CY, Bjorkman DJ, Jensen DM, Kuipers EJ, Lanas A. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018. Gut. 2018 Oct;67(10):1757-1768. doi: 10.1136/gutjnl-2018-316276. Epub 2018 Apr 24. Erratum In: Gut. 2019 Feb;68(2):380.
PMID: 29691276
citation: Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7;2010(7):CD005415. doi: 10.1002/14651858.CD005415.pub3.
PMID: 20614440
citation: Cook D, Guyatt G. Prophylaxis against Upper Gastrointestinal Bleeding in Hospitalized Patients. N Engl J Med. 2018 Jun 28;378(26):2506-2516. doi: 10.1056/NEJMra1605507. No abstract available.
PMID: 29949497
responsible party type: Principal Investigator
investigator affiliation: Samsung Changwon Hospital
investigator full name: Jung Won Lee
investigator title: Professor
mesh term: Peptic Ulcer
mesh term: Peptic Ulcer Hemorrhage
mesh term: Ulcer
mesh term: Hemorrhage