<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/NCT02241044</url>
  </required_header>
  <id_info>
    <org_study_id>VGHKS98-CT8-13</org_study_id>
    <nct_id>NCT02241044</nct_id>
  </id_info>
  <brief_title>Argon Plasma Coagulation for Bleeding Peptic Ulcers</brief_title>
  <official_title>Ivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Veterans General Hospital.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Veterans General Hospital.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      A second endoscopic method added to injection therapy is recommended for high-risk bleeding&#xD;
      peptic ulcers. Many endoscopic devices have been proved as useful hemostatic instruments,&#xD;
      whereas the hemostatic efficacy of argon plasma coagulation (APC) has not been widely&#xD;
      investigated.&#xD;
&#xD;
      Aim:&#xD;
&#xD;
      This study was designed to know whether additional APC treatment could influence the&#xD;
      hemostatic efficacy after endoscopic injection therapy in treating high-risk bleeding ulcers.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      From October 2010 to January 2012, eligible patients who had high-risk bleeding ulcers were&#xD;
      admitted to our hospital. They prospectively randomly underwent either APC therapy plus&#xD;
      distilled water injection or distilled water injection alone. Pantoprazole infusion was&#xD;
      conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer&#xD;
      healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients&#xD;
      who did not benefit from retreatment underwent emergency surgery or transarterial&#xD;
      embolization (TAE).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients and methods Study cohort Patients with acute upper gastrointestinal bleeding (AUGIB)&#xD;
      who were admitted to Kaohsiung Veterans General Hospital between January 2011 and January&#xD;
      2012 were screened. Inclusion criteria were (i) over 20 years of age and (ii) patients with&#xD;
      high-risk peptic ulcer bleeding. Acute hemorrhage from upper gastrointestine was defined as&#xD;
      classical presentation with hematemesis, coffee-ground emesis, and/or melena. High-risk&#xD;
      bleeding ulcers were defined as participants with stigmata of a bleeding visible vessels (eg,&#xD;
      spurting, oozing), a non-bleeding visible vessels (NBVV) or adherent clot.4 A NBVV at&#xD;
      endoscopy was defined as a raised red, red-blue or pale hemispheric vessel protruding from&#xD;
      the ulcer bed, without active bleeding. An adherent clot was defined as an overlying blood&#xD;
      clot that was resistant to vigorous irrigation.&#xD;
&#xD;
      Exclusion criteria were as follows: (i) the presence of another possible bleeding site (eg,&#xD;
      gastroesophageal varix, gastric cancer, reflux esophagitis); (ii) coexistence of actively&#xD;
      severe ill diseases (eg, septic shock, stroke, myocardial infarction, surgical abdomen);&#xD;
      (iii) treatment with an anticoagulant (eg, warfarin); (iv) pregnancy; (v) the presence of&#xD;
      operated stomach or; (vi) refusal to participate in the study.&#xD;
&#xD;
      In current study, baseline characteristics of both study groups were collected at the first&#xD;
      24 hours after admission. Some definitions of events were expressed herein: smoking was&#xD;
      defined as inhalation of smoke from burning tobacco daily in recent 3 months; habitual&#xD;
      consumption of alcohol was defined as participants imbibing alcohol twice or more per week in&#xD;
      recent 3 months; shock was considered systolic blood pressure less than 90 mm Hg or diastolic&#xD;
      less than 60 mmHg, and heart rate over 100 beats per minute; comorbid diseases included&#xD;
      unresolved malignancy, diabetes mellitus, liver cirrhosis, uremia, congestive heart failure,&#xD;
      chronic pulmonary obstructive disease and pneumonia; and coagulopathy was defined as&#xD;
      prothrombin time &gt; 14 seconds and/or activated partial thromboplastin time &gt; 45 seconds.&#xD;
&#xD;
      Randomization In this prospective, parallel-group, randomized controlled trial, eligible&#xD;
      patients were randomized into two groups using opaque-sealed envelopes numbered according to&#xD;
      a table of random numbers before the fist therapeutic endoscopy (index endoscopy): the&#xD;
      Combined group and the Injection group. Informed consent was obtained from each enrolled&#xD;
      participant. Combined group patients received APC therapy following distilled water injection&#xD;
      at index endoscopy. Injection group patients underwent distilled water alone at index&#xD;
      endoscopy. Thereafter both treatment groups were treated with intravenous pantoprazole&#xD;
      (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days,&#xD;
      followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until&#xD;
      the end of 56-day study period. Primary end point was rebleeding. Secondary end points&#xD;
      included initial hemostasis, the need for surgery, transfusion requirements, the period of&#xD;
      hospitalization, severe adverse event (stricture, obstruction or perforation) and death at 30&#xD;
      days postrandomization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2010</start_date>
  <completion_date type="Actual">January 2012</completion_date>
  <primary_completion_date type="Actual">January 2012</primary_completion_date>
  <phase>Phase 4</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</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Rebleeding was observed for a 30-day study period. One or more the following criteria were considered as evidence of recurrent bleeding: aspiration of fresh blood from a nasogastric or orogastric tube; pulse rate over 100 beats per minute; a drop in systolic blood pressure exceeding 30 mmHg; or continue coffee ground emesis or melena with a decline in hemoglobin of at least 2g/dL.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>up to 30 days</time_frame>
    <description>All-cause deaths were recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgery</measure>
    <time_frame>up to 30 days</time_frame>
    <description>the need for surgery wihtin 30 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sever adverse events</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Namely, stricture, obstruction and perforation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Bleeding Ulcers</condition>
  <arm_group>
    <arm_group_label>the Combined group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Combined group patients received Argon plasma coagulation therapy, PSD-60/Endoplasma (Olympus Corporation, Tokyo, Japan), following distilled water injection at index endoscopy. Then participants were treated with intravenous pantoprazole (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days, followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until the end of 56-day study period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>the Injection group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Injection group patients underwent distilled water alone at index endoscopy. Then patients were treated with intravenous pantoprazole (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days, followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until the end of 56-day study period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Argon plasma coagulation</intervention_name>
    <description>Argon plasma coagulation therapy was realized by an Olympus electrosurgical unit/APC unit (PSD-60/Endoplasma, Olympus Corporation, Tokyo, Japan), and its catheters were 2.3mm and 3.5 mm equipped with different endoscope channels.7 APC treatment used a coagulation mode at gas flow/power settings of 1.5L/min and 40 watt for duodenal ulcers and 40-60 watt for gastric ulcers.10 Operative distance between the probe and target bleeding ranged from 2 to 8 mm. Air warranted to be sucked frequently at endoscopy in an attempt at decrease of APC-induced smoke and gastric decompensation, with appropriate treatment of high-risk bleeding ulcers.</description>
    <arm_group_label>the Combined group</arm_group_label>
    <other_name>PSD-60/Endoplasma (Olympus Corporation, Tokyo, Japan)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Distilled water</intervention_name>
    <description>Distilled water was then applied in aliquots of 0.5-2.0 mL, at and around the site of target bleeding, up to 25.0 ml if necessary. Injection amount was determined by endoscopists according to ulcer or vessel size and its location.</description>
    <arm_group_label>the Combined group</arm_group_label>
    <arm_group_label>the Injection group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  (i) over 20 years of age and (ii) patients with high-risk peptic ulcer bleeding.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (i) the presence of another possible bleeding site (eg, gastroesophageal varix,&#xD;
             gastric cancer, reflux esophagitis); (ii) coexistence of actively severe ill diseases&#xD;
             (eg, septic shock, stroke, myocardial infarction, surgical abdomen); (iii) treatment&#xD;
             with an anticoagulant (eg, warfarin); (iv) pregnancy; (v) the presence of operated&#xD;
             stomach or; (vi) refusal to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Huay-Min Wang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Gastroenterology, Department of Internal Medicine</name>
      <address>
        <city>Kaohsiung</city>
        <zip>81362</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>September 13, 2014</last_update_submitted>
  <last_update_submitted_qc>September 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kaohsiung Veterans General Hospital.</investigator_affiliation>
    <investigator_full_name>Huay-Min Wang</investigator_full_name>
    <investigator_title>Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung,Taiwan</investigator_title>
  </responsible_party>
  <keyword>argon plasma coagulation, bleeding peptic ulcer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peptic Ulcer</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/NCT02241044
org study id: VGHKS98-CT8-13
nct id: NCT02241044
lead sponsor: 
has dmc: No
Background:

      A second endoscopic method added to injection therapy is recommended for high-risk bleeding
      peptic ulcers. Many endoscopic devices have been proved as useful hemostatic instruments,
      whereas the hemostatic efficacy of argon plasma coagulation (APC) has not been widely
      investigated.

      Aim:

      This study was designed to know whether additional APC treatment could influence the
      hemostatic efficacy after endoscopic injection therapy in treating high-risk bleeding ulcers.

      Methods:

      From October 2010 to January 2012, eligible patients who had high-risk bleeding ulcers were
      admitted to our hospital. They prospectively randomly underwent either APC therapy plus
      distilled water injection or distilled water injection alone. Pantoprazole infusion was
      conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer
      healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients
      who did not benefit from retreatment underwent emergency surgery or transarterial
      embolization (TAE).
Patients and methods Study cohort Patients with acute upper gastrointestinal bleeding (AUGIB)
      who were admitted to Kaohsiung Veterans General Hospital between January 2011 and January
      2012 were screened. Inclusion criteria were (i) over 20 years of age and (ii) patients with
      high-risk peptic ulcer bleeding. Acute hemorrhage from upper gastrointestine was defined as
      classical presentation with hematemesis, coffee-ground emesis, and/or melena. High-risk
      bleeding ulcers were defined as participants with stigmata of a bleeding visible vessels (eg,
      spurting, oozing), a non-bleeding visible vessels (NBVV) or adherent clot.4 A NBVV at
      endoscopy was defined as a raised red, red-blue or pale hemispheric vessel protruding from
      the ulcer bed, without active bleeding. An adherent clot was defined as an overlying blood
      clot that was resistant to vigorous irrigation.

      Exclusion criteria were as follows: (i) the presence of another possible bleeding site (eg,
      gastroesophageal varix, gastric cancer, reflux esophagitis); (ii) coexistence of actively
      severe ill diseases (eg, septic shock, stroke, myocardial infarction, surgical abdomen);
      (iii) treatment with an anticoagulant (eg, warfarin); (iv) pregnancy; (v) the presence of
      operated stomach or; (vi) refusal to participate in the study.

      In current study, baseline characteristics of both study groups were collected at the first
      24 hours after admission. Some definitions of events were expressed herein: smoking was
      defined as inhalation of smoke from burning tobacco daily in recent 3 months; habitual
      consumption of alcohol was defined as participants imbibing alcohol twice or more per week in
      recent 3 months; shock was considered systolic blood pressure less than 90 mm Hg or diastolic
      less than 60 mmHg, and heart rate over 100 beats per minute; comorbid diseases included
      unresolved malignancy, diabetes mellitus, liver cirrhosis, uremia, congestive heart failure,
      chronic pulmonary obstructive disease and pneumonia; and coagulopathy was defined as
      prothrombin time > 14 seconds and/or activated partial thromboplastin time > 45 seconds.

      Randomization In this prospective, parallel-group, randomized controlled trial, eligible
      patients were randomized into two groups using opaque-sealed envelopes numbered according to
      a table of random numbers before the fist therapeutic endoscopy (index endoscopy): the
      Combined group and the Injection group. Informed consent was obtained from each enrolled
      participant. Combined group patients received APC therapy following distilled water injection
      at index endoscopy. Injection group patients underwent distilled water alone at index
      endoscopy. Thereafter both treatment groups were treated with intravenous pantoprazole
      (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days,
      followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until
      the end of 56-day study period. Primary end point was rebleeding. Secondary end points
      included initial hemostasis, the need for surgery, transfusion requirements, the period of
      hospitalization, severe adverse event (stricture, obstruction or perforation) and death at 30
      days postrandomization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: rebleeding
time frame: up to 30 days
description: Rebleeding was observed for a 30-day study period. One or more the following criteria were considered as evidence of recurrent bleeding: aspiration of fresh blood from a nasogastric or orogastric tube; pulse rate over 100 beats per minute; a drop in systolic blood pressure exceeding 30 mmHg; or continue coffee ground emesis or melena with a decline in hemoglobin of at least 2g/dL.
measure: mortality
time frame: up to 30 days
description: All-cause deaths were recorded.
measure: Surgery
time frame: up to 30 days
description: the need for surgery wihtin 30 days
measure: sever adverse events
time frame: up to 30 days
description: Namely, stricture, obstruction and perforation
arm group label: the Combined group
arm group type: Active Comparator
description: The Combined group patients received Argon plasma coagulation therapy, PSD-60/Endoplasma (Olympus Corporation, Tokyo, Japan), following distilled water injection at index endoscopy. Then participants were treated with intravenous pantoprazole (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days, followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until the end of 56-day study period.
arm group label: the Injection group
arm group type: Placebo Comparator
description: Injection group patients underwent distilled water alone at index endoscopy. Then patients were treated with intravenous pantoprazole (Pantoloc i.v., Nycomed GmbH, Singen, Germany) 40 mg every 12 hours during the first 3 days, followed by oral pantoprazole (Pantoloc, Takeda GmbH, Oranienburg, Germany) 40 mg daily until the end of 56-day study period.
intervention type: Device
intervention name: Argon plasma coagulation
description: Argon plasma coagulation therapy was realized by an Olympus electrosurgical unit/APC unit (PSD-60/Endoplasma, Olympus Corporation, Tokyo, Japan), and its catheters were 2.3mm and 3.5 mm equipped with different endoscope channels.7 APC treatment used a coagulation mode at gas flow/power settings of 1.5L/min and 40 watt for duodenal ulcers and 40-60 watt for gastric ulcers.10 Operative distance between the probe and target bleeding ranged from 2 to 8 mm. Air warranted to be sucked frequently at endoscopy in an attempt at decrease of APC-induced smoke and gastric decompensation, with appropriate treatment of high-risk bleeding ulcers.
arm group label: the Combined group
other name: PSD-60/Endoplasma (Olympus Corporation, Tokyo, Japan)
intervention type: Device
intervention name: Distilled water
description: Distilled water was then applied in aliquots of 0.5-2.0 mL, at and around the site of target bleeding, up to 25.0 ml if necessary. Injection amount was determined by endoscopists according to ulcer or vessel size and its location.
arm group label: the Combined group
arm group label: the Injection group
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Huay-Min Wang, MD
role: Principal Investigator
affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Kaohsiung Veterans General Hospital.
investigator full name: Huay-Min Wang
investigator title: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung,Taiwan
mesh term: Peptic Ulcer
mesh term: Ulcer
mesh term: Hemorrhage