<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/NCT03785080</url>
  </required_header>
  <id_info>
    <org_study_id>NOAC-GAP</org_study_id>
    <nct_id>NCT03785080</nct_id>
  </id_info>
  <brief_title>Non-warfarin Oral AntiCoagulant Resumption After Gastrointestinal Bleeding in Atrial Fibrillation Patients</brief_title>
  <acronym>NOAC-GAP</acronym>
  <official_title>Non-warfarin Oral AntiCoagulant Resumption After Gastrointestinal Bleeding in Atrial Fibrillation Patients (NOAC-GAP) - a Randomised Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <has_dmc>No</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>
      Current clinical society guidelines and statements are non-specific and relatively open-ended&#xD;
      regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after&#xD;
      gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the&#xD;
      prophylactic medication for stroke prevention. These patients are at increased risk for&#xD;
      devastating future thromboembolic events including stroke if NOAC is not resumed promptly,&#xD;
      whilst premature resumption of anticoagulants can result in recurrent GIB, haemorrhage,&#xD;
      anaemia, myocardial ischaemia and infarction in those with ischaemic heart disease, and even&#xD;
      death. However, the question as to how early a NOAC can be safely restarted after acute GIB&#xD;
      has not been previously answered, and there remains an important knowledge gap.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The effectiveness and relative safety of NOACs have been demonstrated in large international&#xD;
      studies where reductions in the incidence of stroke in patients with AF have been reported.&#xD;
      However, the benefits of an anticoagulant are offset by increased incident rates of bleeding&#xD;
      including gastrointestinal bleeding (GIB) and, less commonly, intracranial bleeding,&#xD;
      warranting careful anticoagulation management during periods when patients are susceptible to&#xD;
      the risks for bleeding, stroke and thromboembolism.&#xD;
&#xD;
      The exact duration for withholding NOAC after acute GIB is unknown and in general, current&#xD;
      clinical society guidelines and statements are non-specific and relatively open-ended&#xD;
      regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after&#xD;
      gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the&#xD;
      prophylactic medication for stroke prevention. These patients are at increased risk for&#xD;
      devastating future thromboembolic events including stroke if NOAC is not resumed, whilst&#xD;
      premature resumption of anticoagulants can result in recurrent GIB, haemorrhage, anaemia,&#xD;
      myocardial ischaemia and infarction in those with ischaemic heart disease, and even death.&#xD;
&#xD;
      The purpose of this study is to determine if restarting NOAC very early after endoscopic&#xD;
      haemostasis of bleeding peptic ulcer lesions is equivalent to early resumption in AF patients&#xD;
      in terms of safety and efficacy for prevention of recurrent bleeding freedom from GIB&#xD;
      recurrence, while maintaining undiminished benefits in reducing incident rates of systemic&#xD;
      thromboembolism.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 11, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 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 gastrointestinal bleeding</measure>
    <time_frame>30 days</time_frame>
    <description>melaena and/or haematemesis with drop in Hb &gt;2g/dL and confirmation of bleeding by endoscopy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>recurrent gastrointestinal bleeding</measure>
    <time_frame>90 days</time_frame>
    <description>melaena and/or haematemesis with drop in Hb &gt;2g/dL and confirmation of bleeding by endoscopy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic stroke or transient ischaemic attack</measure>
    <time_frame>30 days</time_frame>
    <description>an acute episode of neurologic deficit of presumed vascular or cardioembolic origin; its presence will be confirmed by a member of the neurology service</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic thromboembolism</measure>
    <time_frame>30 days</time_frame>
    <description>any clinical and/or radiographic acute stroke and/or an acute peripheral arterial thromboembolic event including acute limb ischaemia, coronary embolism and arterial thromboembolism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>6 months</time_frame>
    <description>All-cause mortality</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">552</enrollment>
  <condition>Upper Gastrointestinal Bleeding</condition>
  <arm_group>
    <arm_group_label>restart NOAC very early</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>restart NOAC within 24 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>restart NOAC early</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>restart NOAC at 72 - 84 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>restart NOAC very early</intervention_name>
    <description>withhold NOAC less than 24 hours Post OGD</description>
    <arm_group_label>restart NOAC very early</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>restart NOAC early</intervention_name>
    <description>withhold NOAC for 72 to 84 hours Post OGD</description>
    <arm_group_label>restart NOAC early</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  History of AF&#xD;
&#xD;
          -  Taking any kind of NOAC at the time of index acute GIB&#xD;
&#xD;
          -  Acute upper GIB (non-variceal bleeding lesions accounting for the GIB) with or without&#xD;
             endoscopic treatment confirmed endoscopic haemostasis verified by GI specialist&#xD;
&#xD;
          -  Patient or next-of-kin able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant stroke (including TIA) at the time of index GIB&#xD;
&#xD;
          -  Requiring bridging IV heparin therapy&#xD;
&#xD;
          -  Portal hypertension&#xD;
&#xD;
          -  Known bleeding diathesis&#xD;
&#xD;
          -  Other conditions precluding use of NOAC at the time of randomisation&#xD;
&#xD;
               -  Pregnancy&#xD;
&#xD;
               -  Tumour bleeding&#xD;
&#xD;
               -  Antidote administration to reverse anticoagulation effect of NOACs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph SUNG, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CUHK</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bing Yee SUEN, BSN</last_name>
    <phone>+852 3505 2640</phone>
    <email>suenbingyee@cuhk.edu.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ming Yeung HO, BSc</last_name>
    <phone>+852 2637 1398</phone>
    <email>andrewho@cuhk.edu.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raymond KWOK, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Endoscopy Center, Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph SUNG, MD</last_name>
      <phone>+852 3505 3132</phone>
      <email>jjysung@cuhk.edu.hk</email>
    </contact>
    <contact_backup>
      <last_name>Bing Yee SUEN, BSN</last_name>
      <phone>+852 3505 2640</phone>
      <email>suenbingyee@cuhk.edu.hk</email>
    </contact_backup>
    <investigator>
      <last_name>Joseph SUNG, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Erik FUNG, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jimmy SO</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Hong Kong</country>
    <country>Singapore</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>May 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>May 4, 2020</last_update_submitted>
  <last_update_submitted_qc>May 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 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>Joseph JY SUNG</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>gastrointestinal bleeding</keyword>
  <keyword>stroke</keyword>
  <keyword>thromboembolism</keyword>
  <keyword>atrial fibrillation</keyword>
  <keyword>NOAC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Hemorrhage</mesh_term>
    <mesh_term>Atrial Fibrillation</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/NCT03785080
org study id: NOAC-GAP
nct id: NCT03785080
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Current clinical society guidelines and statements are non-specific and relatively open-ended
      regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after
      gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the
      prophylactic medication for stroke prevention. These patients are at increased risk for
      devastating future thromboembolic events including stroke if NOAC is not resumed promptly,
      whilst premature resumption of anticoagulants can result in recurrent GIB, haemorrhage,
      anaemia, myocardial ischaemia and infarction in those with ischaemic heart disease, and even
      death. However, the question as to how early a NOAC can be safely restarted after acute GIB
      has not been previously answered, and there remains an important knowledge gap.
The effectiveness and relative safety of NOACs have been demonstrated in large international
      studies where reductions in the incidence of stroke in patients with AF have been reported.
      However, the benefits of an anticoagulant are offset by increased incident rates of bleeding
      including gastrointestinal bleeding (GIB) and, less commonly, intracranial bleeding,
      warranting careful anticoagulation management during periods when patients are susceptible to
      the risks for bleeding, stroke and thromboembolism.

      The exact duration for withholding NOAC after acute GIB is unknown and in general, current
      clinical society guidelines and statements are non-specific and relatively open-ended
      regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after
      gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the
      prophylactic medication for stroke prevention. These patients are at increased risk for
      devastating future thromboembolic events including stroke if NOAC is not resumed, whilst
      premature resumption of anticoagulants can result in recurrent GIB, haemorrhage, anaemia,
      myocardial ischaemia and infarction in those with ischaemic heart disease, and even death.

      The purpose of this study is to determine if restarting NOAC very early after endoscopic
      haemostasis of bleeding peptic ulcer lesions is equivalent to early resumption in AF patients
      in terms of safety and efficacy for prevention of recurrent bleeding freedom from GIB
      recurrence, while maintaining undiminished benefits in reducing incident rates of systemic
      thromboembolism.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: recurrent gastrointestinal bleeding
time frame: 30 days
description: melaena and/or haematemesis with drop in Hb >2g/dL and confirmation of bleeding by endoscopy.
measure: recurrent gastrointestinal bleeding
time frame: 90 days
description: melaena and/or haematemesis with drop in Hb >2g/dL and confirmation of bleeding by endoscopy.
measure: Ischemic stroke or transient ischaemic attack
time frame: 30 days
description: an acute episode of neurologic deficit of presumed vascular or cardioembolic origin; its presence will be confirmed by a member of the neurology service
measure: Systemic thromboembolism
time frame: 30 days
description: any clinical and/or radiographic acute stroke and/or an acute peripheral arterial thromboembolic event including acute limb ischaemia, coronary embolism and arterial thromboembolism
measure: Death
time frame: 6 months
description: All-cause mortality
arm group label: restart NOAC very early
arm group type: Experimental
description: restart NOAC within 24 hours
arm group label: restart NOAC early
arm group type: Active Comparator
description: restart NOAC at 72 - 84 hours
intervention type: Other
intervention name: restart NOAC very early
description: withhold NOAC less than 24 hours Post OGD
arm group label: restart NOAC very early
intervention type: Other
intervention name: restart NOAC early
description: withhold NOAC for 72 to 84 hours Post OGD
arm group label: restart NOAC early
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Joseph SUNG, MD
role: Principal Investigator
affiliation: CUHK
last name: Bing Yee SUEN, BSN
phone: +852 3505 2640
email: suenbingyee@cuhk.edu.hk
last name: Ming Yeung HO, BSc
phone: +852 2637 1398
email: andrewho@cuhk.edu.hk
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
country: Australia
country: Hong Kong
country: Singapore
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Joseph JY SUNG
investigator title: Professor
mesh term: Gastrointestinal Hemorrhage
mesh term: Atrial Fibrillation
mesh term: Hemorrhage