<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/NCT01675076</url>
  </required_header>
  <id_info>
    <org_study_id>UOHI-05</org_study_id>
    <nct_id>NCT01675076</nct_id>
  </id_info>
  <brief_title>Strategy of Continued Versus Interrupted Novel Oral Anti-coagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial Thromboembolic Events</brief_title>
  <acronym>BRUISECONTROL2</acronym>
  <official_title>A Randomized Controlled Trial to Investigate Whether a Strategy of Continued Versus Interrupted Novel Oral Anti-coagulant at the Time of Device Surgery, in Patients With Moderate to High Risk of Arterial Thrombo-embolic Events, Leads to a Reduction in the Incidence of Clinically Significant Hematoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Heart Institute Research Corporation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Heart and Stroke Foundation of Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ottawa Heart Institute Research Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the best strategy to manage novel oral&#xD;
      anti-coagulants (NOACs) at the time of pacemaker or defibrillator surgery. The Investigators&#xD;
      hypothesize that performing device surgery without interruption of the novel oral&#xD;
      anti-coagulant will result in a reduced rate of clinically significant hematoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, open-label, randomized trial, with 1:1 randomization to either&#xD;
      continued NOAC or interrupted NOAC in patients with non-rheumatic atrial fibrillation or&#xD;
      atrial flutter and at moderate to high risk of arterial thrombo-embolic events who require&#xD;
      device surgery.&#xD;
&#xD;
      All patients in the study will be receiving Dabigatran or Rivaroxaban or Apixaban for at&#xD;
      least 5 days prior to enrollment. The peri-operative management of the NOAC the patient is&#xD;
      receiving is randomized to Interrupted NOAC or Continued NOAC.&#xD;
&#xD;
      Interrupted NOAC arm:&#xD;
&#xD;
        1. Interrupted Dabigatran&#xD;
&#xD;
             -  based on renal function, patients will discontinue Dabigatran 1 day before surgery&#xD;
                if GFR &gt; 50 mL/min, and 2 days before surgery if GFR is 30-50 mL/min.&#xD;
&#xD;
             -  Dabigatran will be resumed at the next regular dose time, &gt; or = 24 hours after the&#xD;
                end of surgery.&#xD;
&#xD;
        2. Interrupted Rivaroxaban&#xD;
&#xD;
             -  patients will discontinue Rivaroxaban 1 full day before surgery.&#xD;
&#xD;
             -  Rivaroxaban will be resumed at the next regular dose time, &gt; or = 24 hours after&#xD;
                the end of surgery.&#xD;
&#xD;
        3. Interrupted Apixaban&#xD;
&#xD;
             -  patients will discontinue Apixaban 1 full day before surgery.&#xD;
&#xD;
             -  Apixaban will be resumed at the next regular dose time, &gt; or = 24 hours after the&#xD;
                end of surgery.&#xD;
&#xD;
      Continued NOAC arm:&#xD;
&#xD;
      -patients will continue their chronic dose of Dabigatran or Rivaroxaban or Apixaban&#xD;
      throughout.&#xD;
&#xD;
      All patients will have a baseline clinical lab test of serum creatinine or GRF measured.&#xD;
&#xD;
      Patients will be seen post-op on the day of their surgery for assessment of the surgical site&#xD;
      and each day throughout their hospital stay by a blinded member of the research team. A&#xD;
      telephone follow-up will be done on day 3-4 post surgery by an unblinded team member. All&#xD;
      patients are seen 1-2 weeks post-op at their first routine post-op device clinic visit, for&#xD;
      surgical site assessment by the blinded assessor and to complete Quality of Life&#xD;
      questionnaires. Patients will be seen for assessment in the case of any bleeding or&#xD;
      development of pocket swelling or hematoma. Patients developing a hematoma will be followed&#xD;
      until resolution of the hematoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>Phase 3</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinically significant hematoma</measure>
    <time_frame>2 weeks post-op or until resolution of hematoma</time_frame>
    <description>Defined as:&#xD;
Hematoma requiring re-operation&#xD;
- Defined as a hematoma that continues to expand despite all appropriate non-operative measures, or is producing impending or actual wound breakdown or skin necrosis. Minor hematomas that are evacuated at the time of other re-operation (eg. for lead repositioning) are not considered as a primary outcome.&#xD;
or&#xD;
Hematoma resulting in prolongation of hospitalization&#xD;
- Defined as extended hospitalization or rehospitalization for &gt; 24 hours, post index surgery, primarily due to hematoma.&#xD;
or&#xD;
Hematoma requiring interruption of anti-coagulation. - Defined as reversal or intentional withholding of all anticoagulation for &gt; or = 24 hours, in response to wound hematoma.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite of major peri-operative bleeding events and thrombo-embolic events</measure>
    <time_frame>2 weeks post-op</time_frame>
    <description>Each of the components of the primary outcome&#xD;
Composite of all other major peri-operative bleeding events defined as:&#xD;
hemothorax&#xD;
cardiac tamponade&#xD;
significant pericardial effusion&#xD;
Thrombo-embolic events defined as:&#xD;
transient ischemic attack&#xD;
stroke&#xD;
deep venous thrombosis&#xD;
pulmonary embolism&#xD;
peripheral embolus to limb&#xD;
peripheral embolus to other major organ&#xD;
All cause mortality&#xD;
Cost utilization&#xD;
Patient quality of life and peri-operative pain, and satisfaction</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">663</enrollment>
  <condition>Hematoma</condition>
  <arm_group>
    <arm_group_label>Continued NOAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Interrupted NOAC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Interrupted Dabigatran:&#xD;
Discontinue Dabigatran 1 day before surgery if GFR &gt; 50 mL/min or discontinue 2 days before surgery if GFR 30-50 mL/min&#xD;
Resume Dabigatran at next regular dose timing &gt;or = 24 hours after the end of surgery&#xD;
Interrupted Rivaroxaban:&#xD;
Discontinue Rivaroxaban 1 full day before surgery&#xD;
Resume Rivaroxaban at next regular dose timing &gt;or = 24 hours after the end of surgery&#xD;
Interrupted Apixaban:&#xD;
Discontinue Apixaban 1 full day before surgery&#xD;
Resume Apixaban at next regular dose timing &gt;or = 24 hours after the end of surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran</intervention_name>
    <description>NOAC</description>
    <arm_group_label>Continued NOAC</arm_group_label>
    <arm_group_label>Interrupted NOAC</arm_group_label>
    <other_name>Pradaxa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban</intervention_name>
    <description>NOAC</description>
    <arm_group_label>Continued NOAC</arm_group_label>
    <arm_group_label>Interrupted NOAC</arm_group_label>
    <other_name>Xarelto</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban</intervention_name>
    <description>NOAC</description>
    <arm_group_label>Continued NOAC</arm_group_label>
    <arm_group_label>Interrupted NOAC</arm_group_label>
    <other_name>Eliquis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  any patient undergoing device surgery (ie. de novo device implant or pulse generator&#xD;
             change or lead replacement or pocket revision)&#xD;
&#xD;
          -  receiving Dabigatran or Rivaroxaban or Apixaban for at least 5 days prior to&#xD;
             enrollment&#xD;
&#xD;
          -  non-rheumatic atrial fibrillation and/or atrial flutter at moderate or high risk of&#xD;
             ATE defined as: i) CHA2DS2VASc score greater than or equal to 2 OR ii) CHA2DS2VASc&#xD;
             score &lt; 2 with plan for cardioversion or defibrillation threshold testing at time of&#xD;
             device surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  unable or unwilling to provide informed consent&#xD;
&#xD;
          -  history of noncompliance of medical therapy&#xD;
&#xD;
          -  active device infection&#xD;
&#xD;
          -  eGFR &lt; 30 mL/min&#xD;
&#xD;
          -  contraindication to NOAC&#xD;
&#xD;
          -  rheumatic valvular disease with hemodynamically significant valve lesion&#xD;
&#xD;
          -  mechanical heart valve&#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>David Birnie, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Heart Institute Research Corporation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vidal Essebag, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeff Healey, MD</last_name>
    <role>Study Chair</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta-ECAT Group</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T5H 3V9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Victoria Cardiac Arrhythmia Trials Inc.</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8T 1Z4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences General Campus</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 2X2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southlake Regional Health Centre</name>
      <address>
        <city>Newmarket</city>
        <state>Ontario</state>
        <zip>L3Y 2P9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ottawa Heart Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4W7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rouge Valley Health System-Centenary Campus</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M1E 4B9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Humber River Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M3M 0B2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Heart Institute</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H1T 1C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Universite de Montreal (CHUM), Hotel Dieu</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1T8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre/Montreal General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Sacre-Coeur</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4J 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Sherbrooke-Hopital Fleurimont</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>JiH 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie de Quebec</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galilee Medical Center</name>
      <address>
        <city>Nahariya</city>
        <zip>22100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Israel</country>
  </location_countries>
  <results_reference>
    <citation>Birnie DH, Healey JS, Wells GA, Ayala-Paredes F, Coutu B, Sumner GL, Becker G, Verma A, Philippon F, Kalfon E, Eikelboom J, Sandhu RK, Nery PB, Lellouche N, Connolly SJ, Sapp J, Essebag V. Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2). Eur Heart J. 2018 Nov 21;39(44):3973-3979. doi: 10.1093/eurheartj/ehy413.</citation>
    <PMID>30462279</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <last_update_submitted>October 2, 2019</last_update_submitted>
  <last_update_submitted_qc>October 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hematoma</keyword>
  <keyword>novel oral anti-coagulant (NOAC)</keyword>
  <keyword>Device surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Apixaban</mesh_term>
    <mesh_term>Dabigatran</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/NCT01675076
org study id: UOHI-05
nct id: NCT01675076
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine the best strategy to manage novel oral
      anti-coagulants (NOACs) at the time of pacemaker or defibrillator surgery. The Investigators
      hypothesize that performing device surgery without interruption of the novel oral
      anti-coagulant will result in a reduced rate of clinically significant hematoma.
This is a prospective, open-label, randomized trial, with 1:1 randomization to either
      continued NOAC or interrupted NOAC in patients with non-rheumatic atrial fibrillation or
      atrial flutter and at moderate to high risk of arterial thrombo-embolic events who require
      device surgery.

      All patients in the study will be receiving Dabigatran or Rivaroxaban or Apixaban for at
      least 5 days prior to enrollment. The peri-operative management of the NOAC the patient is
      receiving is randomized to Interrupted NOAC or Continued NOAC.

      Interrupted NOAC arm:

        1. Interrupted Dabigatran

             -  based on renal function, patients will discontinue Dabigatran 1 day before surgery
                if GFR > 50 mL/min, and 2 days before surgery if GFR is 30-50 mL/min.

             -  Dabigatran will be resumed at the next regular dose time, > or = 24 hours after the
                end of surgery.

        2. Interrupted Rivaroxaban

             -  patients will discontinue Rivaroxaban 1 full day before surgery.

             -  Rivaroxaban will be resumed at the next regular dose time, > or = 24 hours after
                the end of surgery.

        3. Interrupted Apixaban

             -  patients will discontinue Apixaban 1 full day before surgery.

             -  Apixaban will be resumed at the next regular dose time, > or = 24 hours after the
                end of surgery.

      Continued NOAC arm:

      -patients will continue their chronic dose of Dabigatran or Rivaroxaban or Apixaban
      throughout.

      All patients will have a baseline clinical lab test of serum creatinine or GRF measured.

      Patients will be seen post-op on the day of their surgery for assessment of the surgical site
      and each day throughout their hospital stay by a blinded member of the research team. A
      telephone follow-up will be done on day 3-4 post surgery by an unblinded team member. All
      patients are seen 1-2 weeks post-op at their first routine post-op device clinic visit, for
      surgical site assessment by the blinded assessor and to complete Quality of Life
      questionnaires. Patients will be seen for assessment in the case of any bleeding or
      development of pocket swelling or hematoma. Patients developing a hematoma will be followed
      until resolution of the hematoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Clinically significant hematoma
time frame: 2 weeks post-op or until resolution of hematoma
description: Defined as:
Hematoma requiring re-operation
- Defined as a hematoma that continues to expand despite all appropriate non-operative measures, or is producing impending or actual wound breakdown or skin necrosis. Minor hematomas that are evacuated at the time of other re-operation (eg. for lead repositioning) are not considered as a primary outcome.
or
Hematoma resulting in prolongation of hospitalization
- Defined as extended hospitalization or rehospitalization for > 24 hours, post index surgery, primarily due to hematoma.
or
Hematoma requiring interruption of anti-coagulation. - Defined as reversal or intentional withholding of all anticoagulation for > or = 24 hours, in response to wound hematoma.
measure: Composite of major peri-operative bleeding events and thrombo-embolic events
time frame: 2 weeks post-op
description: Each of the components of the primary outcome
Composite of all other major peri-operative bleeding events defined as:
hemothorax
cardiac tamponade
significant pericardial effusion
Thrombo-embolic events defined as:
transient ischemic attack
stroke
deep venous thrombosis
pulmonary embolism
peripheral embolus to limb
peripheral embolus to other major organ
All cause mortality
Cost utilization
Patient quality of life and peri-operative pain, and satisfaction
arm group label: Continued NOAC
arm group type: Experimental
description: - Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout
arm group label: Interrupted NOAC
arm group type: Active Comparator
description: Interrupted Dabigatran:
Discontinue Dabigatran 1 day before surgery if GFR > 50 mL/min or discontinue 2 days before surgery if GFR 30-50 mL/min
Resume Dabigatran at next regular dose timing >or = 24 hours after the end of surgery
Interrupted Rivaroxaban:
Discontinue Rivaroxaban 1 full day before surgery
Resume Rivaroxaban at next regular dose timing >or = 24 hours after the end of surgery
Interrupted Apixaban:
Discontinue Apixaban 1 full day before surgery
Resume Apixaban at next regular dose timing >or = 24 hours after the end of surgery
intervention type: Drug
intervention name: Dabigatran
description: NOAC
arm group label: Continued NOAC
arm group label: Interrupted NOAC
other name: Pradaxa
intervention type: Drug
intervention name: Rivaroxaban
description: NOAC
arm group label: Continued NOAC
arm group label: Interrupted NOAC
other name: Xarelto
intervention type: Drug
intervention name: Apixaban
description: NOAC
arm group label: Continued NOAC
arm group label: Interrupted NOAC
other name: Eliquis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Birnie, MD
role: Principal Investigator
affiliation: Ottawa Heart Institute Research Corporation
last name: Vidal Essebag, MD
role: Principal Investigator
affiliation: McGill University
last name: Jeff Healey, MD
role: Study Chair
affiliation: McMaster University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Israel
citation: Birnie DH, Healey JS, Wells GA, Ayala-Paredes F, Coutu B, Sumner GL, Becker G, Verma A, Philippon F, Kalfon E, Eikelboom J, Sandhu RK, Nery PB, Lellouche N, Connolly SJ, Sapp J, Essebag V. Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2). Eur Heart J. 2018 Nov 21;39(44):3973-3979. doi: 10.1093/eurheartj/ehy413.
PMID: 30462279
responsible party type: Sponsor
mesh term: Hematoma
mesh term: Rivaroxaban
mesh term: Apixaban
mesh term: Dabigatran