<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/NCT01722786</url>
  </required_header>
  <id_info>
    <org_study_id>RADOA-Registry</org_study_id>
    <nct_id>NCT01722786</nct_id>
  </id_info>
  <brief_title>Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists</brief_title>
  <acronym>RADOA</acronym>
  <official_title>Prospective, Observational, Non-interventional Open-label Multicenter Registry Regarding the Management of Severe Bleeding and/or Urgent Interventions During Treatment With Direct Oral Anticoagulants or Vitamin K Antagonists</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardioangiologisches Centrum Bethanien</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Greifswald</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Dresden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Aachen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Goethe University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Schleswig-Holstein</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vivantes Netzwerk für Gesundheit GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ruhr University of Bochum</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Technische Universität Dresden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Städtisches Klinikum Dresden-Friedrichstadt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cardioangiologisches Centrum Bethanien</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients treated with Vitamin K antagonists (VKA) or direct oral anticoagulants as&#xD;
      Rivaroxaban, Apixaban, Edoxaban or Dabigatran, who experience severe bleeding and/or need&#xD;
      urgent interventions/operations that cannot wait are included in this registry, or during&#xD;
      emergency operations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Registry will offer the opportunity to evaluate the effects of reversal agents as PCC,&#xD;
      aPCC, rVIIa, specific antidots in e.g. severe bleeding patients treated with oral&#xD;
      anticoagulants.&#xD;
&#xD;
      By collecting case reports from several university hospitals and clinics, different treatment&#xD;
      strategies in clinical practice will be observed and evaluated, and may serve as a&#xD;
      comprehensive information resource for the safe management with DOA, but also with the&#xD;
      long-term anticoagulation based on coumarin derivatives in the near future.&#xD;
&#xD;
      The current objective of this registry is to:&#xD;
&#xD;
        1. Document the clinical course and outcome of various clinical bleeding events associated&#xD;
           with DOA or VKA in patients with severe life-threatening bleeding making intervention&#xD;
           necessary&#xD;
&#xD;
        2. Document the clinical course and outcome of urgent surgical interventions within 24&#xD;
           hours after admission in patients under DOA or VKA treatment.&#xD;
&#xD;
        3. Characterisation of therapeutic strategies in stopping acute life-threatening bleeding&#xD;
           including following agents and methods:&#xD;
&#xD;
             1. blood transfusion,&#xD;
&#xD;
             2. platelet concentrates&#xD;
&#xD;
             3. reversal agents [e.g. vitamin K, prothrombin complex concentrate (PCC), activated&#xD;
                PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen&#xD;
                plasma (FFP)]&#xD;
&#xD;
             4. specific antidots, e.g. idarucizumab&#xD;
&#xD;
             5. haemodialysis&#xD;
&#xD;
             6. desmopressin&#xD;
&#xD;
             7. tranexamic acid&#xD;
&#xD;
             8. no specific treatment in respect to the above mentioned treatments (e.g. stop of&#xD;
                medication and waiting until anticoagulant effect of DOA is decreased).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">July 9, 2019</completion_date>
  <primary_completion_date type="Actual">June 30, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome</measure>
    <time_frame>open</time_frame>
    <description>Primary observation points (for all patients):&#xD;
In hospital mortality up to 30 days after admission&#xD;
Secondary observation points (group of patients with life threatening bleeding under oral anticoagulation)&#xD;
Stop of bleeding defined according to the treating physicians&#xD;
Fatality rate caused by unstoppable bleeding&#xD;
Use versus no use of reversal agents - difference in outcome?&#xD;
Definition of supportive measures being effective in stopping bleeding&#xD;
Effectiveness of specific antidots&#xD;
Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding&#xD;
Causality assessment: Relation of SAE to anticoagulant medication</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome</measure>
    <time_frame>open</time_frame>
    <description>Secondary observation points (group of patients with acute surgery under oral anticoagulation)&#xD;
Blood loss, number of transfusions necessary&#xD;
Satisfaction of surgeon during and after surgery concerning bleeding&#xD;
Use versus no use of reversal agents - difference in blood loss and number of transfusions?&#xD;
Use versus no use of reversal agents - difference in satisfaction of surgeon using a standardized questionnaire&#xD;
Causality assessment: Relation of SAE to anticoagulant medication&#xD;
Delay in performance of surgery due to anticoagulation</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">272</enrollment>
  <condition>Severe Bleeding</condition>
  <condition>Urgent Surgery</condition>
  <arm_group>
    <arm_group_label>DOA</arm_group_label>
    <description>Expected number of patients estimated by study duration&#xD;
N= 90 patients treated with direct oral anticoagulants (DOA) with acute bleeding&#xD;
N= 40 patients treated with direct oral anticoagulants (DOA) with urgent surgical intervention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>VKA</arm_group_label>
    <description>Expected number of patients estimated by study duration&#xD;
N= 90 treated with vitamin K antagonists (VKA) with acute bleeding&#xD;
N= 40 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      If possible, left-over from plasma samples (&quot;retention sample&quot;) should be used to perform&#xD;
      further analyses as drug concentrations. Retention samples of very low volume would suffice&#xD;
      for HPLC (information on collection method needed) to assess plasma concentrations of&#xD;
      anticoagulants in these patients.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Expected number of patients estimated by study duration&#xD;
&#xD;
        N= 90 patients treated with direct oral anticoagulants (DOA) with acute bleeding N= 90&#xD;
        treated with vitamin K antagonists (VKA) with acute bleeding&#xD;
&#xD;
        N= 40 patients treated with direct oral anticoagulants (DOA) with urgent surgical&#xD;
        intervention N= 40 patients treated with vitamin K antagonists (VKA) with urgent surgical&#xD;
        intervention&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Patient Eligibility&#xD;
&#xD;
          1. a) Bleeding patients:&#xD;
&#xD;
             Anticoagulated patients with DOA or VKA with clinically overt major bleeding according&#xD;
             to a specified ISTH definition for non-surgical patients:&#xD;
&#xD;
               -  Symptomatic bleeding in a critical area or organ, such as intracranial,&#xD;
                  intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or&#xD;
                  intramuscular with compartment syndrome&#xD;
&#xD;
               -  Bleeding causing a fall in hemoglobin level of 2 g L-1 (1.24 mmol L-1 ) or more&#xD;
                  leading to transfusion of two or more units of whole blood or red cells.&#xD;
&#xD;
             OR b) Acute surgical need Patients treated with DOA or VKA and who need urgent&#xD;
             operation which cannot wait (&lt; 24 h after last intake of drug)&#xD;
&#xD;
             AND&#xD;
&#xD;
          2. with or without reversal agent use (e.g. PCC, aPCC, rVIIa) (and/or haemodialysis for&#xD;
             dabigatran)&#xD;
&#xD;
             AND&#xD;
&#xD;
          3. provides informed consent after the acute event&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cardioangiology Center Bethanien (CCB)</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60389</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Lindhoff-Last E, Herrmann E, Lindau S, Konstantinides S, Grottke O, Nowak-Goettl U, Lucks J, Zydek B, Heymann CV, Birschmann I, Sumnig A, Beyer-Westendorf J, Schellong S, Meybohm P, Greinacher A. Severe Hemorrhage Associated With Oral Anticoagulants. Dtsch Arztebl Int. 2020 May 1;117(18):312-319. doi: 10.3238/arztebl.2020.0312.</citation>
    <PMID>32605708</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 5, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cardioangiologisches Centrum Bethanien</investigator_affiliation>
    <investigator_full_name>Prof. Dr. med. E. Lindhoff-Last</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <keyword>severe bleeding</keyword>
  <keyword>dabigatran</keyword>
  <keyword>rivaroxaban</keyword>
  <keyword>apixaban</keyword>
  <keyword>edoxaban</keyword>
  <keyword>PCC</keyword>
  <keyword>aPCC</keyword>
  <keyword>rVIIa</keyword>
  <keyword>hemodialysis</keyword>
  <keyword>antidots</keyword>
  <keyword>idarucizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</mesh_term>
  </condition_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/NCT01722786
org study id: RADOA-Registry
nct id: NCT01722786
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Patients treated with Vitamin K antagonists (VKA) or direct oral anticoagulants as
      Rivaroxaban, Apixaban, Edoxaban or Dabigatran, who experience severe bleeding and/or need
      urgent interventions/operations that cannot wait are included in this registry, or during
      emergency operations.
The Registry will offer the opportunity to evaluate the effects of reversal agents as PCC,
      aPCC, rVIIa, specific antidots in e.g. severe bleeding patients treated with oral
      anticoagulants.

      By collecting case reports from several university hospitals and clinics, different treatment
      strategies in clinical practice will be observed and evaluated, and may serve as a
      comprehensive information resource for the safe management with DOA, but also with the
      long-term anticoagulation based on coumarin derivatives in the near future.

      The current objective of this registry is to:

        1. Document the clinical course and outcome of various clinical bleeding events associated
           with DOA or VKA in patients with severe life-threatening bleeding making intervention
           necessary

        2. Document the clinical course and outcome of urgent surgical interventions within 24
           hours after admission in patients under DOA or VKA treatment.

        3. Characterisation of therapeutic strategies in stopping acute life-threatening bleeding
           including following agents and methods:

             1. blood transfusion,

             2. platelet concentrates

             3. reversal agents [e.g. vitamin K, prothrombin complex concentrate (PCC), activated
                PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen
                plasma (FFP)]

             4. specific antidots, e.g. idarucizumab

             5. haemodialysis

             6. desmopressin

             7. tranexamic acid

             8. no specific treatment in respect to the above mentioned treatments (e.g. stop of
                medication and waiting until anticoagulant effect of DOA is decreased).
observational model: Cohort
time perspective: Prospective
measure: Primary Outcome
time frame: open
description: Primary observation points (for all patients):
In hospital mortality up to 30 days after admission
Secondary observation points (group of patients with life threatening bleeding under oral anticoagulation)
Stop of bleeding defined according to the treating physicians
Fatality rate caused by unstoppable bleeding
Use versus no use of reversal agents - difference in outcome?
Definition of supportive measures being effective in stopping bleeding
Effectiveness of specific antidots
Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
Causality assessment: Relation of SAE to anticoagulant medication
measure: Secondary Outcome
time frame: open
description: Secondary observation points (group of patients with acute surgery under oral anticoagulation)
Blood loss, number of transfusions necessary
Satisfaction of surgeon during and after surgery concerning bleeding
Use versus no use of reversal agents - difference in blood loss and number of transfusions?
Use versus no use of reversal agents - difference in satisfaction of surgeon using a standardized questionnaire
Causality assessment: Relation of SAE to anticoagulant medication
Delay in performance of surgery due to anticoagulation
arm group label: DOA
description: Expected number of patients estimated by study duration
N= 90 patients treated with direct oral anticoagulants (DOA) with acute bleeding
N= 40 patients treated with direct oral anticoagulants (DOA) with urgent surgical intervention
arm group label: VKA
description: Expected number of patients estimated by study duration
N= 90 treated with vitamin K antagonists (VKA) with acute bleeding
N= 40 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention
If possible, left-over from plasma samples ("retention sample") should be used to perform
      further analyses as drug concentrations. Retention samples of very low volume would suffice
      for HPLC (information on collection method needed) to assess plasma concentrations of
      anticoagulants in these patients.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
country: Germany
citation: Lindhoff-Last E, Herrmann E, Lindau S, Konstantinides S, Grottke O, Nowak-Goettl U, Lucks J, Zydek B, Heymann CV, Birschmann I, Sumnig A, Beyer-Westendorf J, Schellong S, Meybohm P, Greinacher A. Severe Hemorrhage Associated With Oral Anticoagulants. Dtsch Arztebl Int. 2020 May 1;117(18):312-319. doi: 10.3238/arztebl.2020.0312.
PMID: 32605708
responsible party type: Principal Investigator
investigator affiliation: Cardioangiologisches Centrum Bethanien
investigator full name: Prof. Dr. med. E. Lindhoff-Last
investigator title: M.D.
mesh term: Hemorrhage
sharing ipd: No