<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/NCT02197039</url>
  </required_header>
  <id_info>
    <org_study_id>A-ER-103-112</org_study_id>
    <nct_id>NCT02197039</nct_id>
  </id_info>
  <brief_title>The Selection Criteria for the Second-look Endoscopy Among Patients With Bleeding Peptic Ulcers</brief_title>
  <acronym>CSE</acronym>
  <official_title>The Selection Criteria for Deciding Who Needs the Second-look Endoscopy Among Patients With Bleeding Peptic Ulcers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cheng-Kung University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Science Council, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cheng-Kung University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this prospective study is to identify risk factors which could predict poor&#xD;
      fading of SRH or early recurrent bleeding of peptic ulcer hemorrhage after successful&#xD;
      endoscopic hemostasis and high-dose PPI infusion. These risk factors will be the selection&#xD;
      criteria for patients who are indicated to receive second-look endoscopy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peptic ulcer bleeding is a common disease, and recurrent bleeding is an independent risk&#xD;
      factor leading to mortality. The appearance of stigmata of recent hemorrhage (SRH) indicates&#xD;
      possible recurrence of peptic ulcer bleeding, for which the likelihood decreases over the&#xD;
      course of 3-6 days. In addition to endoscopic evidences illustrating the SRH, patients with&#xD;
      co-morbidities have a higher risk of recurrent bleeding.&#xD;
&#xD;
      Patients with co-morbidities have not only higher recurrent bleeding rates during the first 3&#xD;
      days but also higher delay recurrent bleeding after 3-day proton pump inhibitor (PPI)&#xD;
      infusion than those without. More than 50% recurrent bleeding develops after 3-day PPI&#xD;
      infusion among patients with end stage renal diseases. Although endoscopic treatment plus a&#xD;
      72-hour intravenous PPI infusion and followed by oral PPI has already been adopted as a&#xD;
      standard treatment in peptic ulcer bleeding currently, several studies showed limited&#xD;
      effectiveness of such treatment for high risk patients. The reasons may be because lesions of&#xD;
      SRH were not completely faded after initial treatment including endoscopic hemostasis and&#xD;
      intravenous PPI infusion. Thus, it is an important issue to improve such high recurrent&#xD;
      bleeding risk for these patients.&#xD;
&#xD;
      Endoscopic treatment plus a 72-hour intravenous PPI infusion is the standard protocol for&#xD;
      treatment of peptic ulcer bleeding. Moreover, several studies have shown that PPI treatment&#xD;
      could decrease the presentation of SRH. However, there were insufficient data to validate the&#xD;
      efficacy of such standard treatment to fade the SRH, especially among high risk patients.&#xD;
      Therefore, several studies looked at the efficacy of routine second-look endoscopy, defined&#xD;
      as scheduled repeat endoscopy after primary endoscopic hemostasis in patients at high risk of&#xD;
      rebleeding. However, the role and the selection criteria for patients who require second-look&#xD;
      endoscopy remains uncertain. There is a pressing need to elucidate the role of second-look&#xD;
      endoscopy in these patients.&#xD;
&#xD;
      Hence, the purpose of this prospective study is to identify risk factors which could predict&#xD;
      poor fading of SRH or early recurrent bleeding of peptic ulcer hemorrhage after successful&#xD;
      endoscopic hemostasis and high-dose PPI infusion. This data will show the originality and&#xD;
      clinical importance to identify the selection criteria for patients who are indicated to&#xD;
      receive second-look endoscopy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Days</target_duration>
  <primary_outcome>
    <measure>the fading rate of major stigmata of recent hemorrhage</measure>
    <time_frame>within 3 days after the index gastroscopy</time_frame>
    <description>At the index gastroscopy, bleeding ulcers are checked. All of the major stigmata of recent hemorrhage (SRH) are treated by one or a combination of endoscopic therapies. The success of endoscopic hemostasis is defined as cessation of bleeding together with achievement of cavitation at the vessel after application of the heater probe.&#xD;
Second-look endoscopy is scheduled 48-72 hours after successful index endoscopic hemostasis and intravenous high-dose proton pump inhibitor infusion. For each patient with either suspected or active recurrent bleeding, emergent endoscopy is conducted earlier before the schedule to confirm peptic ulcer recurrent bleeding.&#xD;
Possible risk factors including patient's baseline clinical, laboratory characteristics, and gastroscopic pictures are obtained at the time of admission.&#xD;
Multiple logistic regression analysis is applied to assess the independent risk factors related to residual major stigmata or early recurrent bleeding of peptic ulcers.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">316</enrollment>
  <condition>Peptic Ulcer Hemorrhage</condition>
  <arm_group>
    <arm_group_label>The High risk group</arm_group_label>
    <description>Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole or pantoprazole immediately after successful endoscopic hemostasis. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole or pantoprazole infusion.&#xD;
Patients are defined in the high risk group if they still have major stigmata of recent hemorrhage at the second-look endoscopy or have early recurrent bleeding before the schedule time for follow-up.&#xD;
Recurrent bleeding is defined as: 1) continuous melena, hematochezia, or the presence of recurrent bloody aspirates through a nasogastric tube and 2) relapse of hemodynamic instability, including systolic blood pressure &lt;90 mmHg, heart rate &gt;120 beats per minute, or a drop in hemoglobin concentration by more than 2 g/dL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>The control group</arm_group_label>
    <description>Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole or pantoprazole immediately after successful endoscopic hemostasis. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole or pantoprazole infusion.&#xD;
Patients are defined in the control group if they does not have recurrent bleeding before the schedule time for follow-up, and have only minor stigmata of hemorrhage or clean ulcer base at the second-look endoscopy.&#xD;
Recurrent bleeding is defined as: 1) continuous melena, hematochezia, or the presence of recurrent bloody aspirates through a nasogastric tube and 2) relapse of hemodynamic instability, including systolic blood pressure &lt;90 mmHg, heart rate &gt;120 beats per minute, or a drop in hemoglobin concentration by more than 2 g/dL.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>esomeprazole or pantoprazole</intervention_name>
    <description>Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden) immediately after hemostasis is achieved spontaneously or by gastroscopy. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole infusion. Because of concern for patient safety with certain drug-drug interactions, patients who take clopidogrel receive intravenous pantoprazole (Pantoloc®, Takeda, Singen, Germany), including an 80 mg loading dose and a 3-day continuous high-dose (8 mg/h) of infusion.</description>
    <arm_group_label>The High risk group</arm_group_label>
    <arm_group_label>The control group</arm_group_label>
    <other_name>Nexium® (AstraZeneca AB) or Pantoloc® (Takeda)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endoscopic hemostasis</intervention_name>
    <description>At the index gastroscopy, bleeding ulcers are checked. If the adherent clot is found over the ulcer base, it will be vigorously washed away with water jet. All of the stigmata of recent hemorrhage (SRH) are treated by one or a combination of endoscopic therapies including local injection of diluted epinephrine 1:10000, bipolar heated probe at 20 J per goal consecutively until achievement of coaptive coagulation, argon plasma coagulation, band ligation, or hemoclip therapy. The success of endoscopic hemostasis is defined as cessation of bleeding together with achievement of cavitation at the vessel after application of the heater probe.</description>
    <arm_group_label>The High risk group</arm_group_label>
    <arm_group_label>The control group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood, serum, white cells, gastric tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        We developed the study with data collected in an audit of admissions for acute peptic ulcer&#xD;
        hemorrhage at the inpatient wards of National Cheng Kung University Hospital, a tertiary&#xD;
        health care center in Tainan, Taiwan. Patients who receive gastroscopy for melena,&#xD;
        hematochezia, or hematemesis in whom bleeding peptic ulcers with major stigmata of recent&#xD;
        hemorrhage are detected are consecutively enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Bleeding peptic ulcers with major stigmata of recent hemorrhage&#xD;
&#xD;
          -  All of these major SRH are treated by local injection of diluted epinephrine 1:10000&#xD;
             with or without combined therapy with a heater probe, argon plasma coagulation, band&#xD;
             ligation, or hemoclip therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bleeding due to tumor or cancer&#xD;
&#xD;
          -  Bleeding due to the presence of a Dieulafoy lesion&#xD;
&#xD;
          -  Ulcer bleeding due to mechanical factors (i.e., gastrostomy tube induction)&#xD;
&#xD;
          -  Proton pump inhibitors use within one week before enrollment&#xD;
&#xD;
          -  Failure to establish hemostasis under gastroscopy&#xD;
&#xD;
          -  Hypersensitivity to esomeprazole, pantoprazole, or any component of the formulation&#xD;
&#xD;
          -  Previously participated in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bor-Shyang Sheu, MD</last_name>
    <role>Study Director</role>
    <affiliation>National Cheng-Kung University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 20, 2014</study_first_submitted>
  <study_first_submitted_qc>July 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>July 24, 2022</last_update_submitted>
  <last_update_submitted_qc>July 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peptic ulcer hemorrhage, second-look endoscopy</keyword>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esomeprazole</mesh_term>
    <mesh_term>Pantoprazole</mesh_term>
    <mesh_term>Hemostatics</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/NCT02197039
org study id: A-ER-103-112
nct id: NCT02197039
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this prospective study is to identify risk factors which could predict poor
      fading of SRH or early recurrent bleeding of peptic ulcer hemorrhage after successful
      endoscopic hemostasis and high-dose PPI infusion. These risk factors will be the selection
      criteria for patients who are indicated to receive second-look endoscopy.
Peptic ulcer bleeding is a common disease, and recurrent bleeding is an independent risk
      factor leading to mortality. The appearance of stigmata of recent hemorrhage (SRH) indicates
      possible recurrence of peptic ulcer bleeding, for which the likelihood decreases over the
      course of 3-6 days. In addition to endoscopic evidences illustrating the SRH, patients with
      co-morbidities have a higher risk of recurrent bleeding.

      Patients with co-morbidities have not only higher recurrent bleeding rates during the first 3
      days but also higher delay recurrent bleeding after 3-day proton pump inhibitor (PPI)
      infusion than those without. More than 50% recurrent bleeding develops after 3-day PPI
      infusion among patients with end stage renal diseases. Although endoscopic treatment plus a
      72-hour intravenous PPI infusion and followed by oral PPI has already been adopted as a
      standard treatment in peptic ulcer bleeding currently, several studies showed limited
      effectiveness of such treatment for high risk patients. The reasons may be because lesions of
      SRH were not completely faded after initial treatment including endoscopic hemostasis and
      intravenous PPI infusion. Thus, it is an important issue to improve such high recurrent
      bleeding risk for these patients.

      Endoscopic treatment plus a 72-hour intravenous PPI infusion is the standard protocol for
      treatment of peptic ulcer bleeding. Moreover, several studies have shown that PPI treatment
      could decrease the presentation of SRH. However, there were insufficient data to validate the
      efficacy of such standard treatment to fade the SRH, especially among high risk patients.
      Therefore, several studies looked at the efficacy of routine second-look endoscopy, defined
      as scheduled repeat endoscopy after primary endoscopic hemostasis in patients at high risk of
      rebleeding. However, the role and the selection criteria for patients who require second-look
      endoscopy remains uncertain. There is a pressing need to elucidate the role of second-look
      endoscopy in these patients.

      Hence, the purpose of this prospective study is to identify risk factors which could predict
      poor fading of SRH or early recurrent bleeding of peptic ulcer hemorrhage after successful
      endoscopic hemostasis and high-dose PPI infusion. This data will show the originality and
      clinical importance to identify the selection criteria for patients who are indicated to
      receive second-look endoscopy.
observational model: Case-Control
time perspective: Prospective
measure: the fading rate of major stigmata of recent hemorrhage
time frame: within 3 days after the index gastroscopy
description: At the index gastroscopy, bleeding ulcers are checked. All of the major stigmata of recent hemorrhage (SRH) are treated by one or a combination of endoscopic therapies. The success of endoscopic hemostasis is defined as cessation of bleeding together with achievement of cavitation at the vessel after application of the heater probe.
Second-look endoscopy is scheduled 48-72 hours after successful index endoscopic hemostasis and intravenous high-dose proton pump inhibitor infusion. For each patient with either suspected or active recurrent bleeding, emergent endoscopy is conducted earlier before the schedule to confirm peptic ulcer recurrent bleeding.
Possible risk factors including patient's baseline clinical, laboratory characteristics, and gastroscopic pictures are obtained at the time of admission.
Multiple logistic regression analysis is applied to assess the independent risk factors related to residual major stigmata or early recurrent bleeding of peptic ulcers.
arm group label: The High risk group
description: Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole or pantoprazole immediately after successful endoscopic hemostasis. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole or pantoprazole infusion.
Patients are defined in the high risk group if they still have major stigmata of recent hemorrhage at the second-look endoscopy or have early recurrent bleeding before the schedule time for follow-up.
Recurrent bleeding is defined as: 1) continuous melena, hematochezia, or the presence of recurrent bloody aspirates through a nasogastric tube and 2) relapse of hemodynamic instability, including systolic blood pressure <90 mmHg, heart rate >120 beats per minute, or a drop in hemoglobin concentration by more than 2 g/dL.
arm group label: The control group
description: Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole or pantoprazole immediately after successful endoscopic hemostasis. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole or pantoprazole infusion.
Patients are defined in the control group if they does not have recurrent bleeding before the schedule time for follow-up, and have only minor stigmata of hemorrhage or clean ulcer base at the second-look endoscopy.
Recurrent bleeding is defined as: 1) continuous melena, hematochezia, or the presence of recurrent bloody aspirates through a nasogastric tube and 2) relapse of hemodynamic instability, including systolic blood pressure <90 mmHg, heart rate >120 beats per minute, or a drop in hemoglobin concentration by more than 2 g/dL.
intervention type: Drug
intervention name: esomeprazole or pantoprazole
description: Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden) immediately after hemostasis is achieved spontaneously or by gastroscopy. Patients then receive a 3-day continuous high dose (8 mg per hour) of esomeprazole infusion. Because of concern for patient safety with certain drug-drug interactions, patients who take clopidogrel receive intravenous pantoprazole (Pantoloc®, Takeda, Singen, Germany), including an 80 mg loading dose and a 3-day continuous high-dose (8 mg/h) of infusion.
arm group label: The High risk group
arm group label: The control group
other name: Nexium® (AstraZeneca AB) or Pantoloc® (Takeda)
intervention type: Procedure
intervention name: Endoscopic hemostasis
description: At the index gastroscopy, bleeding ulcers are checked. If the adherent clot is found over the ulcer base, it will be vigorously washed away with water jet. All of the stigmata of recent hemorrhage (SRH) are treated by one or a combination of endoscopic therapies including local injection of diluted epinephrine 1:10000, bipolar heated probe at 20 J per goal consecutively until achievement of coaptive coagulation, argon plasma coagulation, band ligation, or hemoclip therapy. The success of endoscopic hemostasis is defined as cessation of bleeding together with achievement of cavitation at the vessel after application of the heater probe.
arm group label: The High risk group
arm group label: The control group
whole blood, serum, white cells, gastric tissue
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 95 Years
healthy volunteers: No
last name: Bor-Shyang Sheu, MD
role: Study Director
affiliation: National Cheng-Kung University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Peptic Ulcer
mesh term: Peptic Ulcer Hemorrhage
mesh term: Ulcer
mesh term: Hemorrhage
mesh term: Esomeprazole
mesh term: Pantoprazole
mesh term: Hemostatics