xml: <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/NCT06000943</url>
    </required_header>
    <id_info>
      <org_study_id>F1R</org_study_id>
      <nct_id>NCT06000943</nct_id>
    </id_info>
    <brief_title>Ischemic And Bleeding Risk Assessment After TAVR</brief_title>
    <acronym>FOCUS ONE</acronym>
    <official_title>Ischemic And Bleeding Risk Assessment After TAVR (FOCUS ONE Registry)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Niguarda Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Niguarda Hospital</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>
        Transcatheter aortic valve replacement (TAVR) represents an effective treatment to improve&#xD;
        symptoms and prognosis in patients with symptomatic severe aortic stenosis (AS) (1-2).&#xD;
  &#xD;
        Giving an established uniform approach towards anticoagulation and antithrombotic therapy&#xD;
        after TAVR in the post POPULAR-TAVI era, recent data coming from the analysis of different&#xD;
        trials, highlight the relevance of the patient's background on the occurrence of ischemic and&#xD;
        bleeding events.&#xD;
  &#xD;
        Despite this a targeted antithrombotic strategy remains unexplored and all patients&#xD;
        undergoing TAVR without other indication to DAPT or OAC, were currently treated according&#xD;
        with the concept of &quot;less is more&quot; (only SAPT or only OAC) regardless the risk level (5-6).&#xD;
  &#xD;
        The keys points of the project will be 1) the assessment of ischemic and bleeding risk after&#xD;
        TAVR stratified according with antithrombotic therapy and surgical risk; 2) the evaluation of&#xD;
        the impact of prostheses type and the complete blood count variables (hemoglobine and&#xD;
        platelets) on the daily average ischemic and bleeding risk and 3) the evaluation of the&#xD;
        dynamic therapeutic changes after TAVR during the follow up.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Nowadays in the post POPULAR-TAVI era, after transcatheter aortic valve replacement (TAVR),&#xD;
        an establish uniform approach towards anticoagulation and antithrombotic therapy were&#xD;
        established.&#xD;
  &#xD;
        All patients undergoing TAVR without other indication to dual antiplatelet therapy (DAPT) or&#xD;
        oral anticoagulation (OAC), were currently treated according with the general concept of&#xD;
        &quot;less is more&quot; (only single antiplatelet therapy - SAPT or only oral anticoagulation - OAC)&#xD;
        [1-3].&#xD;
  &#xD;
        By comparing the frequency of ischemic and bleeding events, data from trial revealed that the&#xD;
        bleeding events were more frequent than the ischemic one despite the level of surgical risk,&#xD;
        however a gradient of reduction in terms of difference was seen from the highest to the&#xD;
        lowest risk profile [4].&#xD;
  &#xD;
        Furthermore, recent literature showed how the timeframe analysis approach, giving the&#xD;
        possibility for a complete time variability evaluation, is able to visualize the fluctuation&#xD;
        of the risk over the time. Unfortunately, no stratified data according with the surgical risk&#xD;
        level, are available using this approach [5].&#xD;
  &#xD;
        Moreover, despite these results that highlight the relevance of the patient's background on&#xD;
        the occurrence of ischemic and bleeding events, a tailored antithrombotic strategy remains&#xD;
        unexplored and all patients undergoing TAVR without other indication to DAPT or OAC, were&#xD;
        currently treated with a uniform approach in terms of intensity during the time (1-3).&#xD;
  &#xD;
        1.1. Assessment of ischemic and bleeding risk after TAVR according with antithrombotic&#xD;
        therapy and surgical risk The rate of adverse thrombotic and hemorrhagic events occurred in&#xD;
        the first days after the procedure, were mainly driven by the TAVR's access bleeding and the&#xD;
        periprocedural stroke.&#xD;
  &#xD;
        Recent study, using the average daily risk analysis, showed the prevalence of the ischemic&#xD;
        risk in the first 30 days after the procedure followed by a rising of the bleeding one which&#xD;
        become predominant during the follow up, affecting the long-term prognosis [5].&#xD;
  &#xD;
        However, only data based on surgical risk derived from the 'first time event approach' are&#xD;
        available in the literature and none of them investigates whether the higher expected risks -&#xD;
        both ischemic and hemorrhagic - in the highest risk cohort remain high even months after&#xD;
        TAVR.&#xD;
  &#xD;
        Bearing this in mind, these observations revealed that ischemic and bleeding events are not&#xD;
        evenly distributed over time, suggesting that a risk-based modulation of the antithrombotic&#xD;
        therapy could be better capture the time-dependent evolution of the phenomena. Experience&#xD;
        from several studies on antithrombotic therapy in the PCI field, have focused on the&#xD;
        intensity and the timing of administration, while no such evidence exists in the field of&#xD;
        TAVR (6-7).&#xD;
  &#xD;
        Thus, the comprehension of this phenomena holds the potential benefit of a tailored&#xD;
        antithrombotic therapy guided by an integrated approach based on the trend of ischemic and&#xD;
        bleeding risk stratified according to the patient's risk profile and the antithrombotic&#xD;
        regimen adopted.&#xD;
  &#xD;
        1.2. Impact of prostheses type and complete blood count variables on ischemic and bleeding&#xD;
        events As the same of patient's features and periprocedural variables, it is possible to&#xD;
        assume that also the prostheses characteristics in terms of type of leaflet (porcine vs&#xD;
        bovine), stent frame amount (short frame versus long frame) and the number of they&#xD;
        (valve-in-valve), are not fully investigated previously and may play a role in the thrombotic&#xD;
        and hemorrhagic adverse events occurrence.&#xD;
  &#xD;
        Understanding the impact of structural and functional valve's characteristics on the bleeding&#xD;
        and ischemic risk among patients who undergo TAVR, may have important implications in&#xD;
        prosthesis and antithrombotic therapy selection and needs to be investigated properly with a&#xD;
        &quot;repeated-event&quot; analysis.&#xD;
  &#xD;
        Moreover, also the frequent phenomenon of anemia and thrombocytopenia after TAVR, were&#xD;
        identified from several studies as predictors of poor outcome up to 1 year follow up even&#xD;
        with a perfect prosthesis function and despite the mechanism behind, it's not completely&#xD;
        understood (8). According to these data the relationship between blood count abnormalities,&#xD;
        type of prosthesis and ischemic and bleeding risk have never been explored.&#xD;
  &#xD;
        The identification of predictive variables leading to the development of anemia and&#xD;
        thrombocytopenia and their impact on the risk of hemorrhagic and thrombotic events, might&#xD;
        allow us a tailored selection of prosthesis, antithrombotic strategy and procedural planning&#xD;
        in order to potentially reduce the risk of adverse events.&#xD;
  &#xD;
        1.3. Dynamic therapeutic changes after TAVI Several studies investigated the impact of&#xD;
        different antithrombotic strategies on outcomes and prosthesis performance by comparing&#xD;
        different approaches in combination. However, most of them assessed the clinical endpoints&#xD;
        considering only the discharge therapy, with a lack of real data in terms of regimes&#xD;
        switching and duration of any effective treatment prescribed.&#xD;
  &#xD;
        The assessment of these data during follow-up, remains underexplored even though their&#xD;
        availability could potentially allow an accurate definition of the ongoing strategy at the&#xD;
        time of adverse event occurrence. Moreover, the collection of these variables may provide&#xD;
        important information about the antithrombotic management, including the reason, the rate and&#xD;
        the timing of crossover for each treatment.&#xD;
  &#xD;
        Finally, given the evolution of the antithrombotic strategy in the last years, in particular&#xD;
        in the pre and post Popular TAVI era, and knowing the therapeutic management during the first&#xD;
        year of follow up, it's possible to define the impact of any study/trial on the real-world&#xD;
        approach in recent years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 15, 2024</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Other</time_perspective>
    </study_design_info>
    <target_duration>3 Years</target_duration>
    <primary_outcome>
      <measure>Trend of average daily ischemic risk (ADIR) and average daily bleeding risk (ADBR)</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>ADIR was calculated as the total number of ischemic events (CV deaths, MI, ischemic stroke and other thrombotic events-including repeat events) divided by the number of patients-day at risk.&#xD;
  ADBR was calculated as the total number of bleeding events (including repeat events) divided by the number of the number of patients-day at risk.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Average daily risks (ADRs) in different type of valve prosthesis</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Average daily risks (ADRs) in different type of valve prosthesis</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average daily risks (ADRs) in anaemic and thrombocytopenic patients</measure>
      <time_frame>In hospital up to 1 year</time_frame>
      <description>Trend and prevalence of ADIR and ADBR in patients who developed anaemia and thrombocytopenia after the procedure and during the hospitalization. Anaemia and thrombocytopenia were defined according to the WHO and EHA guidelines. ADRs were calculated as the total number of events divided by the number of patients-day at risk</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of antithrombotic regimen changes after TAVR</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>Percentage of antithrombotic strategy changes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Timing of antithrombotic regimen changes after TAVR</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>Number of days after the procedure in which the antithrombotic strategy was changed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Type of antithrombotic regimen changes after TAVR</measure>
      <time_frame>At 30-days, 90-days and 1 year</time_frame>
      <description>Type of changes in antithrombotic strategy taking into account all interclass (antiplatelet to anticoagulant or vice versa) and intraclass drugs switches (anticoagulant - VKA to DOAC, antiplatelet - DAPT to SAPT or vice versa)</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">2500</enrollment>
    <condition>Aortic Valve Stenosis</condition>
    <condition>Transcatheter Aortic Valve Replacement</condition>
    <arm_group>
      <arm_group_label>Lower Surgical Risk</arm_group_label>
      <description>Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intermediate Surgical Risk</arm_group_label>
      <description>Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High Surgical Risk</arm_group_label>
      <description>Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Low vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPT</intervention_name>
      <description>All patients undergoing TAVR will be stratified according with surgical risk level and all combination of antithrombotic therapy at discharge&#xD;
  Low risk (SAPT vs DAPT and OAC vs OAC+SAPT) Intermediate risk (SAPT vs DAPT and OAC vs OAC+SAPT) High risk (SAPT vs DAPT and OAC vs OAC+SAPT)</description>
      <arm_group_label>High Surgical Risk</arm_group_label>
      <arm_group_label>Intermediate Surgical Risk</arm_group_label>
      <arm_group_label>Lower Surgical Risk</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Consecutive patients with severe aortic stenosis diagnosed according to ESC guidelines,&#xD;
          undergoing TAVR&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
            -  All patients with severe aortic stenosis undergoing TAVR.&#xD;
  &#xD;
            -  Availability of changes in antithrombotic therapy at 1 month, 90 days, and 1 year&#xD;
               after TAVR.&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
            -  Patients who died during the index procedure&#xD;
  &#xD;
            -  Patients in triple antithrombotic therapy at discharge&#xD;
  &#xD;
            -  Patients with a known prognosis less than 1 year at the time of TAVR&#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_contact>
      <last_name>Giuseppe Esposito, MD</last_name>
      <phone>+393278393131</phone>
      <email>giuseppe.esposito@yahoo.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>OLV Hospital</name>
        <address>
          <city>Aalst</city>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Complejo Asistencial Dr. Sótero del Río</name>
        <address>
          <city>Santiago</city>
          <country>Chile</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Cardiocenter, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady</name>
        <address>
          <city>Prague</city>
          <zip>10034</zip>
          <country>Czechia</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>ASST GOM Niguarda</name>
        <address>
          <city>Milano</city>
          <state>Italia</state>
          <zip>20162</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Giuseppe Esposito, MD</last_name>
        <phone>+393278393131</phone>
        <email>giuseppe.esposito@yahoo.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Humanitas Research Hospital</name>
        <address>
          <city>Rozzano</city>
          <state>Milano</state>
          <zip>20089</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>IRCCS Policlinico San Donato</name>
        <address>
          <city>San Donato Milanese</city>
          <state>Milano</state>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>IRCCS Ospedale Policlinico San Martino</name>
        <address>
          <city>Genova</city>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Ospedale Galeazzi Sant'Ambrogio</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>San Carlo Hospital</name>
        <address>
          <city>Potenza</city>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera Sant'Andrea</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>A.O.U. Città della Salute e della Scienza di Torino</name>
        <address>
          <city>Torino</city>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Puerto Real University Hospital, Puerto Real</name>
        <address>
          <city>Cadiz</city>
          <country>Spain</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>Belgium</country>
      <country>Chile</country>
      <country>Czechia</country>
      <country>Italy</country>
      <country>Spain</country>
    </location_countries>
    <reference>
      <citation>Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. doi: 10.1093/eurheartj/ehab395. No abstract available. Erratum In: Eur Heart J. 2022 Feb 18;:</citation>
      <PMID>34453165</PMID>
    </reference>
    <reference>
      <citation>Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Feb 2;143(5):e35-e71. doi: 10.1161/CIR.0000000000000932. Epub 2020 Dec 17. Erratum In: Circulation. 2021 Feb 2;143(5):e228. Circulation. 2021 Mar 9;143(10):e784.</citation>
      <PMID>33332149</PMID>
    </reference>
    <reference>
      <citation>Ko E, Park DW. Optimal Antithrombotic Strategy After Transcatheter Aortic Valve Replacement: Is the &quot;Less Is More&quot; Concept Always Better? J Am Heart Assoc. 2021 May 4;10(9):e021241. doi: 10.1161/JAHA.121.021241. Epub 2021 Apr 17. No abstract available.</citation>
      <PMID>33870701</PMID>
    </reference>
    <reference>
      <citation>Brouwer J, Nijenhuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Oct 8;383(15):1447-1457. doi: 10.1056/NEJMoa2017815. Epub 2020 Aug 30.</citation>
      <PMID>32865376</PMID>
    </reference>
    <reference>
      <citation>Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Apr 30;382(18):1696-1707. doi: 10.1056/NEJMoa1915152. Epub 2020 Mar 29.</citation>
      <PMID>32223116</PMID>
    </reference>
    <reference>
      <citation>Capodanno D, Collet JP, Dangas G, Montalescot G, Ten Berg JM, Windecker S, Angiolillo DJ. Antithrombotic Therapy After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2021 Aug 9;14(15):1688-1703. doi: 10.1016/j.jcin.2021.06.020.</citation>
      <PMID>34353601</PMID>
    </reference>
    <reference>
      <citation>Esposito G, Montalto C, Crimi G, Grippo R, Morici N, Bruschi G, Testa L, De Marco F, Soriano F, Nava S, Stefanini G, Bedogni F, Oreglia JA. Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry). Int J Cardiol. 2023 Jun 15;381:2-7. doi: 10.1016/j.ijcard.2023.03.009. Epub 2023 Mar 8.</citation>
      <PMID>36898584</PMID>
    </reference>
    <reference>
      <citation>Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019 Nov 21;381(21):2032-2042. doi: 10.1056/NEJMoa1908419. Epub 2019 Sep 26.</citation>
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    </reference>
    <reference>
      <citation>Valgimigli M, Frigoli E, Heg D, Tijssen J, Juni P, Vranckx P, Ozaki Y, Morice MC, Chevalier B, Onuma Y, Windecker S, Tonino PAL, Roffi M, Lesiak M, Mahfoud F, Bartunek J, Hildick-Smith D, Colombo A, Stankovic G, Iniguez A, Schultz C, Kornowski R, Ong PJL, Alasnag M, Rodriguez AE, Moschovitis A, Laanmets P, Donahue M, Leonardi S, Smits PC; MASTER DAPT Investigators. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021 Oct 28;385(18):1643-1655. doi: 10.1056/NEJMoa2108749. Epub 2021 Aug 28.</citation>
      <PMID>34449185</PMID>
    </reference>
    <reference>
      <citation>De Larochelliere H, Puri R, Eikelboom JW, Rodes-Cabau J. Blood Disorders in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review. JACC Cardiovasc Interv. 2019 Jan 14;12(1):1-11. doi: 10.1016/j.jcin.2018.09.041.</citation>
      <PMID>30621965</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 13, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Aortic Valve Stenosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06000943
  org study id: F1R
  nct id: NCT06000943
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Transcatheter aortic valve replacement (TAVR) represents an effective treatment to improve
        symptoms and prognosis in patients with symptomatic severe aortic stenosis (AS) (1-2).
  
        Giving an established uniform approach towards anticoagulation and antithrombotic therapy
        after TAVR in the post POPULAR-TAVI era, recent data coming from the analysis of different
        trials, highlight the relevance of the patient's background on the occurrence of ischemic and
        bleeding events.
  
        Despite this a targeted antithrombotic strategy remains unexplored and all patients
        undergoing TAVR without other indication to DAPT or OAC, were currently treated according
        with the concept of "less is more" (only SAPT or only OAC) regardless the risk level (5-6).
  
        The keys points of the project will be 1) the assessment of ischemic and bleeding risk after
        TAVR stratified according with antithrombotic therapy and surgical risk; 2) the evaluation of
        the impact of prostheses type and the complete blood count variables (hemoglobine and
        platelets) on the daily average ischemic and bleeding risk and 3) the evaluation of the
        dynamic therapeutic changes after TAVR during the follow up.
  Nowadays in the post POPULAR-TAVI era, after transcatheter aortic valve replacement (TAVR),
        an establish uniform approach towards anticoagulation and antithrombotic therapy were
        established.
  
        All patients undergoing TAVR without other indication to dual antiplatelet therapy (DAPT) or
        oral anticoagulation (OAC), were currently treated according with the general concept of
        "less is more" (only single antiplatelet therapy - SAPT or only oral anticoagulation - OAC)
        [1-3].
  
        By comparing the frequency of ischemic and bleeding events, data from trial revealed that the
        bleeding events were more frequent than the ischemic one despite the level of surgical risk,
        however a gradient of reduction in terms of difference was seen from the highest to the
        lowest risk profile [4].
  
        Furthermore, recent literature showed how the timeframe analysis approach, giving the
        possibility for a complete time variability evaluation, is able to visualize the fluctuation
        of the risk over the time. Unfortunately, no stratified data according with the surgical risk
        level, are available using this approach [5].
  
        Moreover, despite these results that highlight the relevance of the patient's background on
        the occurrence of ischemic and bleeding events, a tailored antithrombotic strategy remains
        unexplored and all patients undergoing TAVR without other indication to DAPT or OAC, were
        currently treated with a uniform approach in terms of intensity during the time (1-3).
  
        1.1. Assessment of ischemic and bleeding risk after TAVR according with antithrombotic
        therapy and surgical risk The rate of adverse thrombotic and hemorrhagic events occurred in
        the first days after the procedure, were mainly driven by the TAVR's access bleeding and the
        periprocedural stroke.
  
        Recent study, using the average daily risk analysis, showed the prevalence of the ischemic
        risk in the first 30 days after the procedure followed by a rising of the bleeding one which
        become predominant during the follow up, affecting the long-term prognosis [5].
  
        However, only data based on surgical risk derived from the 'first time event approach' are
        available in the literature and none of them investigates whether the higher expected risks -
        both ischemic and hemorrhagic - in the highest risk cohort remain high even months after
        TAVR.
  
        Bearing this in mind, these observations revealed that ischemic and bleeding events are not
        evenly distributed over time, suggesting that a risk-based modulation of the antithrombotic
        therapy could be better capture the time-dependent evolution of the phenomena. Experience
        from several studies on antithrombotic therapy in the PCI field, have focused on the
        intensity and the timing of administration, while no such evidence exists in the field of
        TAVR (6-7).
  
        Thus, the comprehension of this phenomena holds the potential benefit of a tailored
        antithrombotic therapy guided by an integrated approach based on the trend of ischemic and
        bleeding risk stratified according to the patient's risk profile and the antithrombotic
        regimen adopted.
  
        1.2. Impact of prostheses type and complete blood count variables on ischemic and bleeding
        events As the same of patient's features and periprocedural variables, it is possible to
        assume that also the prostheses characteristics in terms of type of leaflet (porcine vs
        bovine), stent frame amount (short frame versus long frame) and the number of they
        (valve-in-valve), are not fully investigated previously and may play a role in the thrombotic
        and hemorrhagic adverse events occurrence.
  
        Understanding the impact of structural and functional valve's characteristics on the bleeding
        and ischemic risk among patients who undergo TAVR, may have important implications in
        prosthesis and antithrombotic therapy selection and needs to be investigated properly with a
        "repeated-event" analysis.
  
        Moreover, also the frequent phenomenon of anemia and thrombocytopenia after TAVR, were
        identified from several studies as predictors of poor outcome up to 1 year follow up even
        with a perfect prosthesis function and despite the mechanism behind, it's not completely
        understood (8). According to these data the relationship between blood count abnormalities,
        type of prosthesis and ischemic and bleeding risk have never been explored.
  
        The identification of predictive variables leading to the development of anemia and
        thrombocytopenia and their impact on the risk of hemorrhagic and thrombotic events, might
        allow us a tailored selection of prosthesis, antithrombotic strategy and procedural planning
        in order to potentially reduce the risk of adverse events.
  
        1.3. Dynamic therapeutic changes after TAVI Several studies investigated the impact of
        different antithrombotic strategies on outcomes and prosthesis performance by comparing
        different approaches in combination. However, most of them assessed the clinical endpoints
        considering only the discharge therapy, with a lack of real data in terms of regimes
        switching and duration of any effective treatment prescribed.
  
        The assessment of these data during follow-up, remains underexplored even though their
        availability could potentially allow an accurate definition of the ongoing strategy at the
        time of adverse event occurrence. Moreover, the collection of these variables may provide
        important information about the antithrombotic management, including the reason, the rate and
        the timing of crossover for each treatment.
  
        Finally, given the evolution of the antithrombotic strategy in the last years, in particular
        in the pre and post Popular TAVI era, and knowing the therapeutic management during the first
        year of follow up, it's possible to define the impact of any study/trial on the real-world
        approach in recent years.
  observational model: Cohort
  time perspective: Other
  measure: Trend of average daily ischemic risk (ADIR) and average daily bleeding risk (ADBR)
  time frame: At 30-days, 90-days and 1 year
  description: ADIR was calculated as the total number of ischemic events (CV deaths, MI, ischemic stroke and other thrombotic events-including repeat events) divided by the number of patients-day at risk.
  ADBR was calculated as the total number of bleeding events (including repeat events) divided by the number of the number of patients-day at risk.
  measure: Average daily risks (ADRs) in different type of valve prosthesis
  time frame: At 30-days, 90-days and 1 year
  description: Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk
  measure: Average daily risks (ADRs) in different type of valve prosthesis
  time frame: At 30-days, 90-days and 1 year
  description: Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk
  measure: Average daily risks (ADRs) in anaemic and thrombocytopenic patients
  time frame: In hospital up to 1 year
  description: Trend and prevalence of ADIR and ADBR in patients who developed anaemia and thrombocytopenia after the procedure and during the hospitalization. Anaemia and thrombocytopenia were defined according to the WHO and EHA guidelines. ADRs were calculated as the total number of events divided by the number of patients-day at risk
  measure: Rate of antithrombotic regimen changes after TAVR
  time frame: At 30-days, 90-days and 1 year
  description: Percentage of antithrombotic strategy changes
  measure: Timing of antithrombotic regimen changes after TAVR
  time frame: At 30-days, 90-days and 1 year
  description: Number of days after the procedure in which the antithrombotic strategy was changed
  measure: Type of antithrombotic regimen changes after TAVR
  time frame: At 30-days, 90-days and 1 year
  description: Type of changes in antithrombotic strategy taking into account all interclass (antiplatelet to anticoagulant or vice versa) and intraclass drugs switches (anticoagulant - VKA to DOAC, antiplatelet - DAPT to SAPT or vice versa)
  arm group label: Lower Surgical Risk
  description: Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
  arm group label: Intermediate Surgical Risk
  description: Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
  arm group label: High Surgical Risk
  description: Surgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
  intervention type: Other
  intervention name: Low vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPT
  description: All patients undergoing TAVR will be stratified according with surgical risk level and all combination of antithrombotic therapy at discharge
  Low risk (SAPT vs DAPT and OAC vs OAC+SAPT) Intermediate risk (SAPT vs DAPT and OAC vs OAC+SAPT) High risk (SAPT vs DAPT and OAC vs OAC+SAPT)
  arm group label: High Surgical Risk
  arm group label: Intermediate Surgical Risk
  arm group label: Lower Surgical Risk
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Giuseppe Esposito, MD
  phone: +393278393131
  email: giuseppe.esposito@yahoo.com
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  country: Belgium
  country: Chile
  country: Czechia
  country: Italy
  country: Spain
  citation: Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. doi: 10.1093/eurheartj/ehab395. No abstract available. Erratum In: Eur Heart J. 2022 Feb 18;:
  PMID: 34453165
  citation: Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Feb 2;143(5):e35-e71. doi: 10.1161/CIR.0000000000000932. Epub 2020 Dec 17. Erratum In: Circulation. 2021 Feb 2;143(5):e228. Circulation. 2021 Mar 9;143(10):e784.
  PMID: 33332149
  citation: Ko E, Park DW. Optimal Antithrombotic Strategy After Transcatheter Aortic Valve Replacement: Is the "Less Is More" Concept Always Better? J Am Heart Assoc. 2021 May 4;10(9):e021241. doi: 10.1161/JAHA.121.021241. Epub 2021 Apr 17. No abstract available.
  PMID: 33870701
  citation: Brouwer J, Nijenhuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Oct 8;383(15):1447-1457. doi: 10.1056/NEJMoa2017815. Epub 2020 Aug 30.
  PMID: 32865376
  citation: Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Apr 30;382(18):1696-1707. doi: 10.1056/NEJMoa1915152. Epub 2020 Mar 29.
  PMID: 32223116
  citation: Capodanno D, Collet JP, Dangas G, Montalescot G, Ten Berg JM, Windecker S, Angiolillo DJ. Antithrombotic Therapy After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2021 Aug 9;14(15):1688-1703. doi: 10.1016/j.jcin.2021.06.020.
  PMID: 34353601
  citation: Esposito G, Montalto C, Crimi G, Grippo R, Morici N, Bruschi G, Testa L, De Marco F, Soriano F, Nava S, Stefanini G, Bedogni F, Oreglia JA. Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry). Int J Cardiol. 2023 Jun 15;381:2-7. doi: 10.1016/j.ijcard.2023.03.009. Epub 2023 Mar 8.
  PMID: 36898584
  citation: Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019 Nov 21;381(21):2032-2042. doi: 10.1056/NEJMoa1908419. Epub 2019 Sep 26.
  PMID: 31556978
  citation: Valgimigli M, Frigoli E, Heg D, Tijssen J, Juni P, Vranckx P, Ozaki Y, Morice MC, Chevalier B, Onuma Y, Windecker S, Tonino PAL, Roffi M, Lesiak M, Mahfoud F, Bartunek J, Hildick-Smith D, Colombo A, Stankovic G, Iniguez A, Schultz C, Kornowski R, Ong PJL, Alasnag M, Rodriguez AE, Moschovitis A, Laanmets P, Donahue M, Leonardi S, Smits PC; MASTER DAPT Investigators. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021 Oct 28;385(18):1643-1655. doi: 10.1056/NEJMoa2108749. Epub 2021 Aug 28.
  PMID: 34449185
  citation: De Larochelliere H, Puri R, Eikelboom JW, Rodes-Cabau J. Blood Disorders in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review. JACC Cardiovasc Interv. 2019 Jan 14;12(1):1-11. doi: 10.1016/j.jcin.2018.09.041.
  PMID: 30621965
  responsible party type: Sponsor
  mesh term: Aortic Valve Stenosis
  sharing ipd: No