<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/NCT02185027</url>
  </required_header>
  <id_info>
    <org_study_id>DCIC 13 18</org_study_id>
    <nct_id>NCT02185027</nct_id>
  </id_info>
  <brief_title>Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants</brief_title>
  <acronym>GIHP-NACO</acronym>
  <official_title>Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Floralis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Grenoble</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The arrival on the market of direct oral factor Xa and factor IIa inhibitors (dabigatran&#xD;
      (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) and others soon to come) raises novel&#xD;
      questions among clinicians confronted with the emergency management of patients treated with&#xD;
      these new drugs. It is likely that these new oral anticoagulants (NOACs) will eventually win&#xD;
      a significant market share in the indications secondary prevention of venous thromboembolism&#xD;
      and prevention of cardioembolic events in patients with nonvalvular atrial fibrillation, due&#xD;
      to their net clinical benefit and their practicality of use compared with vitamin K&#xD;
      antagonists (VKAs).&#xD;
&#xD;
      However, despite the fact that NOACs reduce the incidence of intracranial bleeding by about&#xD;
      half compared with VKAs, the risk remains significant; furthermore, in clinical trials, these&#xD;
      drugs had little or no effect on reducing the incidence of major extracranial bleeding. In&#xD;
      everyday practice, where the indication could be expanded to unselected populations and due&#xD;
      to a potential for misuse, it is likely that the incidence of bleeding complications will be&#xD;
      higher than that reported in clinical trials. Indeed, the numerous alerts emanating from&#xD;
      regulatory agencies in various countries (US, Australia, etc.) bear witness to this, and&#xD;
      should serve as a reminder that these anticoagulants have a real potential for bleeding&#xD;
      complications and, in the absence of an antidote, there is no validated management strategy.&#xD;
&#xD;
      Furthermore, as these drugs can be prescribed for months or years, patients may eventually be&#xD;
      exposed to situations at high hemorrhagic risk, such as emergency surgery or invasive&#xD;
      procedures, trauma, etc. Analysis of data from the trial : dabigatran versus warfarin in&#xD;
      patients with atrial fibrillation (RE-LY) showed that during the two years of follow-up,&#xD;
      approximately 25% of the patients underwent an invasive procedure, ranging from pacemaker&#xD;
      insertion to major surgery. Thus, a large proportion of patients treated with NOACs are&#xD;
      concerned by this issue.&#xD;
&#xD;
      In anticipation of a gradually increasing influx of patients in a critical situation (active&#xD;
      bleeding or need to rapidly secure hemostasis before an invasive procedure), it is urgent to&#xD;
      define the conduct to adopt based on the experience gained from the earliest cases. This is&#xD;
      the objective of the French-speaking GIHP-NACO observatory set up by the GIHP (French Working&#xD;
      Group on Perioperative Hemostasis).&#xD;
&#xD;
      For the moment, then, the management recommendations derive from expert opinions based on&#xD;
      pharmacokinetic data and on the partial correction of NOAC-induced hypocoagulability by&#xD;
      various nonspecific procoagulants (non-activated or activated prothrombin complex&#xD;
      concentrates, recombinant factor VIIa). These procoagulants are currently used in an&#xD;
      empirical manner to control bleeding, with as many successes as failures reported in the&#xD;
      literature, and their benefit-risk ratio in these patients is therefore uncertain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The management of critical situations is difficult for several reasons:&#xD;
&#xD;
        -  First, there is significant intra- and inter-individual variability in the&#xD;
           pharmacokinetics of NOACs, which is further heightened in the critical setting by drug&#xD;
           interactions with other agents that interfere with P-GLYCOPROTEIN (P-GP) and cytochrome&#xD;
           ( cytochrome P4503A4) in patients who are often elderly and multi medicated, and by&#xD;
           rapid variations in renal function, which is essential for elimination of NOACs.&#xD;
&#xD;
        -  Second, biological guidance is weak: there is no clearcut therapeutic range nor any&#xD;
           validated hemostatic safety cutoff, as is the case with the International Normalized&#xD;
           Ratio (INR) for VKAs. Conventional coagulation tests (PT/aPTT) are poorly standardized&#xD;
           and difficult to interpret. Assays to measure the serum concentrations of these drugs&#xD;
           are not widespread outside of a few teaching hospitals.&#xD;
&#xD;
        -  Third, there is a lack of clinical experience. Analyses of critical situations that&#xD;
           occurred during clinical trials were done after the fact and the data collected are&#xD;
           heterogeneous and incomplete. Clinical cases reported in the literature are rarely well&#xD;
           documented.&#xD;
&#xD;
      The objective of the observatory is to rapidly acquire documented and thorough feedback on&#xD;
      clinical experience with these new drugs that will be able to confer a higher level of&#xD;
      evidence to the management recommendations for treated patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>complications and compliance with GIHP recommendations</measure>
    <time_frame>At 1 month</time_frame>
    <description>Association between the incidence rate at 1 month post-intervention of an event among the following complications and compliance with GIHP recommendations (appended) evaluated by a composite endpoint Major cardiovascular event ( acute coronary syndrome, cardiogenic shock, stroke or Transient Ischemic Attack (TIA), Central Nervous System (extra-CNS) thromboembolic event).&#xD;
Major bleeding event in the group of patients who had an emergency invasive procedure.&#xD;
Continued bleeding after management (treatment, reversal) in the group of patients managed for bleeding.&#xD;
Compliance with GIHP recommendations (appended) evaluated by a composite endpoint based on:&#xD;
Observance of reversal strategies&#xD;
Observance of the therapeutic window between the last administration and the procedure, in cases where the NOAC was stopped</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>NOAC management</measure>
    <time_frame>during the perioperative period</time_frame>
    <description>All NOAC treatments will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>reversal strategies description</measure>
    <time_frame>during the perioperative period</time_frame>
    <description>use or not of reversal strategies will be described</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation test results</measure>
    <time_frame>during the perioperative period</time_frame>
    <description>Coagulation test results will be recorded</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1166</enrollment>
  <condition>Venous Thromboembolism</condition>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>complications and compliance with GIHP recommendations</arm_group_label>
    <description>Description at 1 month post-intervention of an potential event</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>complications and compliance with GIHP recommendations</intervention_name>
    <description>Description of complications, compliance, major bleeding events, treatments, reversal strategies.</description>
    <arm_group_label>complications and compliance with GIHP recommendations</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects managed in view of surgery or an invasive procedure, emergency or not managed and&#xD;
        hospitalized for active bleeding with a long-term therapy (in the indication atrial&#xD;
        fibrillation or treatment of pulmonary embolism or deep vein thrombosis) by one&#xD;
        antithrombotic agent (Dabigatran, Rivaroxaban, Apixaban)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Managed in view of surgery or an invasive procedure, emergency or not&#xD;
&#xD;
          -  Managed and hospitalized for active bleeding&#xD;
&#xD;
          -  Long-term therapy (in the indication atrial fibrillation or treatment of pulmonary&#xD;
             embolism or deep vein thrombosis) by at least one antithrombotic agent from the&#xD;
             following list: DABIGATRAN ETEXILATE MESYLATE or RIVAROXABAN or APIXABAN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Refusal to participate in the study: listed in the non-inclusion registry&#xD;
&#xD;
          -  Antithrombotics indicated for the prevention of venous thromboembolism&#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>Pierre Albaladejo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Grenoble</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Brugmann</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpitaux du Léman</name>
      <address>
        <city>Thonon-les-Bains</city>
        <state>haute-Savoie</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Agen</name>
      <address>
        <city>Agen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU d'Amiens</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Annecy</name>
      <address>
        <city>Annecy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Castres</name>
      <address>
        <city>Castres</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Chambéry</name>
      <address>
        <city>Chambery</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Alpes leman</name>
      <address>
        <city>Contamine-sur-Arve</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Gap</name>
      <address>
        <city>GAP</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Mutualiste Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCL - Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCL - Hôpital de la Croix-Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCL - Lyon Sud</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Marseille</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Emile Gallé - SINCAL</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nancy</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nimes</name>
      <address>
        <city>Nimes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH de Niort</name>
      <address>
        <city>Niort</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP - Antoine Beclere</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP - Tenon</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP Henri Mondor</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP Hôpital Bichat</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP Site St Antoine</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aphp-Hegp</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP-Hôpital Beaujon</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hôpital Américain</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bicêtre</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rennes</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Strasbourg - Hôpital Civil</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital d'Instruction des Armées Sainte-Anne</name>
      <address>
        <city>Toulon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH Voiron</name>
      <address>
        <city>Voiron</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, Blais N, Fontana P, Cohen A, Llau JV, Rosencher N, Schved JF, de Maistre E, Samama MM, Mismetti P, Sie P; Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013. Arch Cardiovasc Dis. 2013 Jun-Jul;106(6-7):382-93. doi: 10.1016/j.acvd.2013.04.009. Epub 2013 Jun 25.</citation>
    <PMID>23810130</PMID>
  </reference>
  <reference>
    <citation>Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012 Aug;108(2):217-24. doi: 10.1160/TH12-03-0179. Epub 2012 May 25. Erratum In: Thromb Haemost. 2013 Jan;109(1):169.</citation>
    <PMID>22627883</PMID>
  </reference>
  <reference>
    <citation>Sie P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, Van der Linden P, Pernod G, Lecompte T, Gouin-Thibault I, Albaladejo P; Working Group on Perioperative Haemostasis; French Study Group on Thrombosis and Haemostasis. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis. 2011 Dec;104(12):669-76. doi: 10.1016/j.acvd.2011.09.001. Epub 2011 Oct 29.</citation>
    <PMID>22152517</PMID>
  </reference>
  <reference>
    <citation>Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012 Jul 17;126(3):343-8. doi: 10.1161/CIRCULATIONAHA.111.090464. Epub 2012 Jun 14. Erratum In: Circulation. 2012 Sep 4;126(10):e160. Heidbuchle, Hein [corrected to Heidbuchel, Hein].</citation>
    <PMID>22700854</PMID>
  </reference>
  <reference>
    <citation>Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625-51. doi: 10.1093/europace/eut083.</citation>
    <PMID>23625942</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>September 28, 2021</last_update_submitted>
  <last_update_submitted_qc>September 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oral anticoagulants</keyword>
  <keyword>Surgery</keyword>
  <keyword>Haemorrhage</keyword>
  <keyword>Emergency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</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/NCT02185027
org study id: DCIC 13 18
nct id: NCT02185027
lead sponsor: 
collaborator: 
has dmc: No
The arrival on the market of direct oral factor Xa and factor IIa inhibitors (dabigatran
      (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) and others soon to come) raises novel
      questions among clinicians confronted with the emergency management of patients treated with
      these new drugs. It is likely that these new oral anticoagulants (NOACs) will eventually win
      a significant market share in the indications secondary prevention of venous thromboembolism
      and prevention of cardioembolic events in patients with nonvalvular atrial fibrillation, due
      to their net clinical benefit and their practicality of use compared with vitamin K
      antagonists (VKAs).

      However, despite the fact that NOACs reduce the incidence of intracranial bleeding by about
      half compared with VKAs, the risk remains significant; furthermore, in clinical trials, these
      drugs had little or no effect on reducing the incidence of major extracranial bleeding. In
      everyday practice, where the indication could be expanded to unselected populations and due
      to a potential for misuse, it is likely that the incidence of bleeding complications will be
      higher than that reported in clinical trials. Indeed, the numerous alerts emanating from
      regulatory agencies in various countries (US, Australia, etc.) bear witness to this, and
      should serve as a reminder that these anticoagulants have a real potential for bleeding
      complications and, in the absence of an antidote, there is no validated management strategy.

      Furthermore, as these drugs can be prescribed for months or years, patients may eventually be
      exposed to situations at high hemorrhagic risk, such as emergency surgery or invasive
      procedures, trauma, etc. Analysis of data from the trial : dabigatran versus warfarin in
      patients with atrial fibrillation (RE-LY) showed that during the two years of follow-up,
      approximately 25% of the patients underwent an invasive procedure, ranging from pacemaker
      insertion to major surgery. Thus, a large proportion of patients treated with NOACs are
      concerned by this issue.

      In anticipation of a gradually increasing influx of patients in a critical situation (active
      bleeding or need to rapidly secure hemostasis before an invasive procedure), it is urgent to
      define the conduct to adopt based on the experience gained from the earliest cases. This is
      the objective of the French-speaking GIHP-NACO observatory set up by the GIHP (French Working
      Group on Perioperative Hemostasis).

      For the moment, then, the management recommendations derive from expert opinions based on
      pharmacokinetic data and on the partial correction of NOAC-induced hypocoagulability by
      various nonspecific procoagulants (non-activated or activated prothrombin complex
      concentrates, recombinant factor VIIa). These procoagulants are currently used in an
      empirical manner to control bleeding, with as many successes as failures reported in the
      literature, and their benefit-risk ratio in these patients is therefore uncertain.
The management of critical situations is difficult for several reasons:

        -  First, there is significant intra- and inter-individual variability in the
           pharmacokinetics of NOACs, which is further heightened in the critical setting by drug
           interactions with other agents that interfere with P-GLYCOPROTEIN (P-GP) and cytochrome
           ( cytochrome P4503A4) in patients who are often elderly and multi medicated, and by
           rapid variations in renal function, which is essential for elimination of NOACs.

        -  Second, biological guidance is weak: there is no clearcut therapeutic range nor any
           validated hemostatic safety cutoff, as is the case with the International Normalized
           Ratio (INR) for VKAs. Conventional coagulation tests (PT/aPTT) are poorly standardized
           and difficult to interpret. Assays to measure the serum concentrations of these drugs
           are not widespread outside of a few teaching hospitals.

        -  Third, there is a lack of clinical experience. Analyses of critical situations that
           occurred during clinical trials were done after the fact and the data collected are
           heterogeneous and incomplete. Clinical cases reported in the literature are rarely well
           documented.

      The objective of the observatory is to rapidly acquire documented and thorough feedback on
      clinical experience with these new drugs that will be able to confer a higher level of
      evidence to the management recommendations for treated patients.
observational model: Cohort
time perspective: Prospective
measure: complications and compliance with GIHP recommendations
time frame: At 1 month
description: Association between the incidence rate at 1 month post-intervention of an event among the following complications and compliance with GIHP recommendations (appended) evaluated by a composite endpoint Major cardiovascular event ( acute coronary syndrome, cardiogenic shock, stroke or Transient Ischemic Attack (TIA), Central Nervous System (extra-CNS) thromboembolic event).
Major bleeding event in the group of patients who had an emergency invasive procedure.
Continued bleeding after management (treatment, reversal) in the group of patients managed for bleeding.
Compliance with GIHP recommendations (appended) evaluated by a composite endpoint based on:
Observance of reversal strategies
Observance of the therapeutic window between the last administration and the procedure, in cases where the NOAC was stopped
measure: NOAC management
time frame: during the perioperative period
description: All NOAC treatments will be recorded
measure: reversal strategies description
time frame: during the perioperative period
description: use or not of reversal strategies will be described
measure: Coagulation test results
time frame: during the perioperative period
description: Coagulation test results will be recorded
arm group label: complications and compliance with GIHP recommendations
description: Description at 1 month post-intervention of an potential event
intervention type: Other
intervention name: complications and compliance with GIHP recommendations
description: Description of complications, compliance, major bleeding events, treatments, reversal strategies.
arm group label: complications and compliance with GIHP recommendations
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pierre Albaladejo, MD
role: Principal Investigator
affiliation: University Hospital, Grenoble
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country: Belgium
country: France
citation: Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, Blais N, Fontana P, Cohen A, Llau JV, Rosencher N, Schved JF, de Maistre E, Samama MM, Mismetti P, Sie P; Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013. Arch Cardiovasc Dis. 2013 Jun-Jul;106(6-7):382-93. doi: 10.1016/j.acvd.2013.04.009. Epub 2013 Jun 25.
PMID: 23810130
citation: Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012 Aug;108(2):217-24. doi: 10.1160/TH12-03-0179. Epub 2012 May 25. Erratum In: Thromb Haemost. 2013 Jan;109(1):169.
PMID: 22627883
citation: Sie P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, Van der Linden P, Pernod G, Lecompte T, Gouin-Thibault I, Albaladejo P; Working Group on Perioperative Haemostasis; French Study Group on Thrombosis and Haemostasis. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis. 2011 Dec;104(12):669-76. doi: 10.1016/j.acvd.2011.09.001. Epub 2011 Oct 29.
PMID: 22152517
citation: Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012 Jul 17;126(3):343-8. doi: 10.1161/CIRCULATIONAHA.111.090464. Epub 2012 Jun 14. Erratum In: Circulation. 2012 Sep 4;126(10):e160. Heidbuchle, Hein [corrected to Heidbuchel, Hein].
PMID: 22700854
citation: Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625-51. doi: 10.1093/europace/eut083.
PMID: 23625942
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Thromboembolism
mesh term: Venous Thromboembolism