<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/NCT03785015</url>
  </required_header>
  <id_info>
    <org_study_id>ReASA</org_study_id>
    <nct_id>NCT03785015</nct_id>
  </id_info>
  <brief_title>When Should Low-dose Aspirin be Resumed After Peptic Ulcer Bleeding?</brief_title>
  <official_title>When Should Low-dose Aspirin be Resumed After Peptic Ulcer Bleeding? A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Friendship Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA)&#xD;
      is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial&#xD;
      infarction, a study of over 14,000 patients reported that the risk of life-threatening GI&#xD;
      bleeding in the first two months is 7 times higher than that in the subsequent months. After&#xD;
      endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases will&#xD;
      need to resume ASA. However, the investigator found that immediate resumption of ASA saves&#xD;
      life but at the expense of higher risk of recurrent bleeding. Peptic ulcer bleeding&#xD;
      associated with ASA is a major cause of hospitalization in Hong Kong. Currently, ASA use has&#xD;
      contributed to about one-third of the bleeding ulcers admitted to our hospital that serves a&#xD;
      local population of 1.5 million. Accordingly, current international guidelines recommend&#xD;
      early resumption of ASA but the optimal timing is unknown. Clinicians often face the dilemma:&#xD;
      when should ASA be resumed? Furthermore, patients who suffer from acute peptic ulcer bleeding&#xD;
      are often elderly patients with significant co-morbidities. Mortality in these patients&#xD;
      remains high. Clinicians are facing an increasing number of patients who are on antiplatelet&#xD;
      drugs or anticoagulants. The investigator proposes a open-label randomized-controlled trial&#xD;
      to evaluate the optimal timing of resuming ASA in patients with CV diseases complicated by&#xD;
      peptic ulcer bleeding. Patients will be randomized to resume the standard treatment within&#xD;
      first few hours or only to resume the standard treatment 72 hours after endoscopic&#xD;
      haemostasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA)&#xD;
      is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial&#xD;
      infarction, a study of over 14,000 patients reported that the risk of life-threatening GI&#xD;
      bleeding in the first two months is 7 times higher than that in the subsequent months (1).&#xD;
      After endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases&#xD;
      will need to resume ASA. Clinicians often face the dilemma: when should ASA be resumed?&#xD;
      Furthermore, patients who suffer from acute peptic ulcer bleeding are often elderly patients&#xD;
      with significant co-morbidities. Mortality in these patients remains high. Clinicians are&#xD;
      facing an increasing number of patients who are on antiplatelet drugs or anticoagulants.&#xD;
&#xD;
      However, there are very limited data to guide the best timing for resumption of ASA in these&#xD;
      high risk patients. To date, our group has conducted the only randomized controlled trial in&#xD;
      the literature that has partially addressed this issue. Importantly, the investigator found&#xD;
      that immediate resumption of ASA saves life but at the expense of higher risk of recurrent&#xD;
      bleeding (2). Accordingly, current international guidelines recommend early resumption of ASA&#xD;
      but the optimal timing is unknown.&#xD;
&#xD;
      In the setting of acute GI bleeding, it is often a dilemma whether to stop or to restart&#xD;
      these drugs. The balance between bleeding and thrombotic risks is difficult and treatment is&#xD;
      often empirical and not evidence-based.&#xD;
&#xD;
      The investigator aims to test the hypothesis that in ASA users complicated by peptic ulcer&#xD;
      bleeding, withholding ASA till day 3 reduces the risk of recurrent bleeding compared to&#xD;
      immediate resumption of ASA without a significant increase in mortality.&#xD;
&#xD;
      References&#xD;
&#xD;
        1. Moukarbel GV, Signorovitch JE, Pfeffer MA et al. Gastrointestinal bleeding in high risk&#xD;
           survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30(18):2226-32.&#xD;
&#xD;
        2. Sung JJ, Lau JY, Ching JY et al. Continuation of low-dose aspirin therapy in peptic&#xD;
           ulcer bleeding: a randomized trial. Ann Intern Med 2010;152(1):1-9.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Anticipated">February 28, 2024</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2024</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrent peptic ulcer bleeding</measure>
    <time_frame>30 days after endoscopic treatment</time_frame>
    <description>Recurrent peptic ulcer bleeding within 30 days of endoscopic treatment</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">436</enrollment>
  <condition>Aspirin</condition>
  <condition>GastroIntestinal Bleeding</condition>
  <arm_group>
    <arm_group_label>Withold aspirin till after endoscopic haemostasis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Withhold the standard treatment of aspirin within 12 hours after endoscopic haemostasis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Withold aspirin till 72 hours</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Withhold the standard treatment of aspirin till 72 after endoscopic haemostasis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Resume Aspirin within 12 hours</intervention_name>
    <description>Resume the standard treatment within 12 hours after endoscopic haemostasis</description>
    <arm_group_label>Withold aspirin till after endoscopic haemostasis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Resume Aspirin 72 - 84 hours</intervention_name>
    <description>Resume the standard treatment between 72 and 84 hours after endoscopic haemostasis</description>
    <arm_group_label>Withold aspirin till 72 hours</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt;18&#xD;
&#xD;
          2. Patients with actively bleeding gastroduodenal lesions (peptic ulcer, bleeding&#xD;
             erosions, or Dieulafoy's lesion) or ulcers showing other high risk stigmata (visible&#xD;
             blood vessels or adherent clots) treated by endoscopic therapy&#xD;
&#xD;
          3. Subjects continue to require regular ASA or dual anti-platelet therapy for treatment&#xD;
             of CV or cerebrovascular diseases after this bleeding episode&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who received ASA for primary prophylaxis&#xD;
&#xD;
          2. Unsuccessful endoscopic hemostasis of bleeding ulcers or ulcer perforation&#xD;
&#xD;
          3. Gastric outlet obstruction&#xD;
&#xD;
          4. Known sensitivity to PPIs&#xD;
&#xD;
          5. Previous partial gastrectomy or vagotomy&#xD;
&#xD;
          6. Patients need concomitant anticoagulant&#xD;
&#xD;
          7. Pregnant unless sterilization, menopause or last menstrual period within 7 days&#xD;
&#xD;
          8. Other co-morbidities or advanced age that will hinder the drug compliance or follow up&#xD;
&#xD;
          9. Malignancy on active treatment&#xD;
&#xD;
         10. Unable to give consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Siew C Ng, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ka Man Kee, MPH</last_name>
    <phone>85235053855</phone>
    <email>carmenkee@cuhk.edu.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jessica Ching, MPH</last_name>
    <phone>85235053524</phone>
    <email>jessicaching@cuhk.edu.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Siew Chien Ng, PhD</last_name>
      <phone>35053996</phone>
      <email>siewchienng@cuhk.edu.hk</email>
    </contact>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</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>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Siew Chien NG</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>Gastrointestinal Hemorrhage</mesh_term>
    <mesh_term>Peptic Ulcer</mesh_term>
    <mesh_term>Peptic Ulcer Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03785015
org study id: ReASA
nct id: NCT03785015
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA)
      is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial
      infarction, a study of over 14,000 patients reported that the risk of life-threatening GI
      bleeding in the first two months is 7 times higher than that in the subsequent months. After
      endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases will
      need to resume ASA. However, the investigator found that immediate resumption of ASA saves
      life but at the expense of higher risk of recurrent bleeding. Peptic ulcer bleeding
      associated with ASA is a major cause of hospitalization in Hong Kong. Currently, ASA use has
      contributed to about one-third of the bleeding ulcers admitted to our hospital that serves a
      local population of 1.5 million. Accordingly, current international guidelines recommend
      early resumption of ASA but the optimal timing is unknown. Clinicians often face the dilemma:
      when should ASA be resumed? Furthermore, patients who suffer from acute peptic ulcer bleeding
      are often elderly patients with significant co-morbidities. Mortality in these patients
      remains high. Clinicians are facing an increasing number of patients who are on antiplatelet
      drugs or anticoagulants. The investigator proposes a open-label randomized-controlled trial
      to evaluate the optimal timing of resuming ASA in patients with CV diseases complicated by
      peptic ulcer bleeding. Patients will be randomized to resume the standard treatment within
      first few hours or only to resume the standard treatment 72 hours after endoscopic
      haemostasis.
Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA)
      is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial
      infarction, a study of over 14,000 patients reported that the risk of life-threatening GI
      bleeding in the first two months is 7 times higher than that in the subsequent months (1).
      After endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases
      will need to resume ASA. Clinicians often face the dilemma: when should ASA be resumed?
      Furthermore, patients who suffer from acute peptic ulcer bleeding are often elderly patients
      with significant co-morbidities. Mortality in these patients remains high. Clinicians are
      facing an increasing number of patients who are on antiplatelet drugs or anticoagulants.

      However, there are very limited data to guide the best timing for resumption of ASA in these
      high risk patients. To date, our group has conducted the only randomized controlled trial in
      the literature that has partially addressed this issue. Importantly, the investigator found
      that immediate resumption of ASA saves life but at the expense of higher risk of recurrent
      bleeding (2). Accordingly, current international guidelines recommend early resumption of ASA
      but the optimal timing is unknown.

      In the setting of acute GI bleeding, it is often a dilemma whether to stop or to restart
      these drugs. The balance between bleeding and thrombotic risks is difficult and treatment is
      often empirical and not evidence-based.

      The investigator aims to test the hypothesis that in ASA users complicated by peptic ulcer
      bleeding, withholding ASA till day 3 reduces the risk of recurrent bleeding compared to
      immediate resumption of ASA without a significant increase in mortality.

      References

        1. Moukarbel GV, Signorovitch JE, Pfeffer MA et al. Gastrointestinal bleeding in high risk
           survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30(18):2226-32.

        2. Sung JJ, Lau JY, Ching JY et al. Continuation of low-dose aspirin therapy in peptic
           ulcer bleeding: a randomized trial. Ann Intern Med 2010;152(1):1-9.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Recurrent peptic ulcer bleeding
time frame: 30 days after endoscopic treatment
description: Recurrent peptic ulcer bleeding within 30 days of endoscopic treatment
arm group label: Withold aspirin till after endoscopic haemostasis
arm group type: Experimental
description: Withhold the standard treatment of aspirin within 12 hours after endoscopic haemostasis.
arm group label: Withold aspirin till 72 hours
arm group type: Active Comparator
description: Withhold the standard treatment of aspirin till 72 after endoscopic haemostasis.
intervention type: Other
intervention name: Resume Aspirin within 12 hours
description: Resume the standard treatment within 12 hours after endoscopic haemostasis
arm group label: Withold aspirin till after endoscopic haemostasis
intervention type: Other
intervention name: Resume Aspirin 72 - 84 hours
description: Resume the standard treatment between 72 and 84 hours after endoscopic haemostasis
arm group label: Withold aspirin till 72 hours
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Siew C Ng, MD
role: Principal Investigator
affiliation: Chinese University of Hong Kong
last name: Ka Man Kee, MPH
phone: 85235053855
email: carmenkee@cuhk.edu.hk
last name: Jessica Ching, MPH
phone: 85235053524
email: jessicaching@cuhk.edu.hk
facility: 
status: Recruiting
contact: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Siew Chien NG
investigator title: Professor
mesh term: Gastrointestinal Hemorrhage
mesh term: Peptic Ulcer
mesh term: Peptic Ulcer Hemorrhage
mesh term: Hemorrhage
mesh term: Aspirin
sharing ipd: No