<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/NCT02224066</url>
  </required_header>
  <id_info>
    <org_study_id>MEIX-VALV-002</org_study_id>
    <secondary_id>REAC TAVI</secondary_id>
    <nct_id>NCT02224066</nct_id>
  </id_info>
  <brief_title>Platelet Reactivity After TAVI: A Multicenter Pilot Study</brief_title>
  <acronym>REAC-TAVI</acronym>
  <official_title>Assessment of Platelet REACtivity After Transcatheter Aortic Valve Implantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Meixoeiro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Meixoeiro</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A high platelet reactivity in patients with severe symptomatic Aortic Stenosis (AS) selected&#xD;
      for TAVI (Transcatheter aortic valve implantation) procedure has been demonstrated&#xD;
      previously, and the use of double antiaggregation therapy (DAPT) with Clopidogrel and&#xD;
      Acetylsalicylic acid (ASA) do not achieve consistent and adequate suppression of platelet&#xD;
      reactivity. The purpose of this study is evaluate the efficacy of ticagrelor alone versus&#xD;
      DAPT with clopidogrel and aspirin for the suppression of high platelet reactivity following&#xD;
      TAVI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2016</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by a system to verify the patient's platelet reactivity (VerifyNow P2Y12 assay).</measure>
    <time_frame>Three months after antiplatelet treatment initiation following procedure.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by VerifyNow P2Y12 assay.</measure>
    <time_frame>Six hours after antiplatelet treatment initiation following procedure.</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Assess the safety of antiplatelet monotherapy with ticagrelor compared to DAPT with aspirin and clopidogrel, with regard to the incidence of investigator-reported clinical events according to predefined criteria, including bleeding definitions.</measure>
    <time_frame>Three months after antiplatelet treatment initiation following procedure.</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">65</enrollment>
  <condition>Severe Aortic Valve Stenosis</condition>
  <condition>Transcatheter Aortic Valve Implantation</condition>
  <condition>Transcatheter Aortic Valve Replacement</condition>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with high-on-treatment platelet reactivity (PRU ≥ 208)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin/Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with high-on-treatment platelet reactivity (PRU ≥ 208)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Registry arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients with normal-on-treatment platelet reactivity (PRU &lt; 208) will continue with Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor 90 mg twice per day during three months following TAVI</intervention_name>
    <arm_group_label>Ticagrelor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI</intervention_name>
    <arm_group_label>Aspirin/Clopidogrel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For inclusion in the study subjects should fulfill the following criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. Adult patients (more than 18 years) with ability to understand and accept the&#xD;
             participation in the clinical trial.&#xD;
&#xD;
          3. Patients with degenerative symptomatic severe AS accepted for TAVI after evaluation of&#xD;
             the Heart Team of each center.&#xD;
&#xD;
          4. Patients who are not participating in any other clinical trial or research study&#xD;
             (registries allowed).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects should not enter the study if any of the following exclusion criteria are&#xD;
        fulfilled:&#xD;
&#xD;
          1. Recent stroke &lt;14 days prior to TAVI, non-revascularized severe coronary or carotid&#xD;
             artery disease (&gt;70% stenosis) or life expectancy &lt; 12 months&#xD;
&#xD;
          2. Patients under chronic oral anticoagulation&#xD;
&#xD;
          3. Patients with proven allergy to aspirin, clopidogrel or ticagrelor&#xD;
&#xD;
          4. Patients that after TAVI cannot undergo a regimen of single or dual antiplatelet&#xD;
             therapy for 3 months due to a new post-TAVI medical indication&#xD;
&#xD;
          5. Known pregnancy or breast-feeding&#xD;
&#xD;
          6. Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A&#xD;
             (CYP3A) that cannot be suspended during the course of the study. Medications&#xD;
             considered as potent inhibitors are: ketoconazole, itraconazole, voriconazole,&#xD;
             telithromycin, clarithromycin (or erythromycin but not astromicin, nefazodone,&#xD;
             ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and more than a daily liter&#xD;
             of grapefruit juice.&#xD;
&#xD;
          7. Thrombocytopenia (&lt;50,000 platelets U/L) well documented and clinically relevant.&#xD;
&#xD;
          8. Patients with documented moderate or severe hepatic insufficiency&#xD;
&#xD;
          9. Any condition that may put the patient at risk or influence the outcome of the trial&#xD;
&#xD;
         10. Patients previously randomized in this trial or in another clinical trial with an&#xD;
             investigational product or device over the past 30 days.&#xD;
&#xD;
         11. Patients who cannot attend follow up visits scheduled in the study&#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>Andrés Iñiguez Romo, MD;Phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Xerencia de Xestión Integrada de Vigo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Victor A Jimenez Diaz, MD; Msc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Xerencia de Xestión Integrada de Vigo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pablo Juan Salvadores, Pharma; MPH</last_name>
    <role>Study Director</role>
    <affiliation>Xerencia xestión integrada de Vigo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Clinic Universitari Bellvitge</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Álvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <state>Pontevedra</state>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Creu i Sant Creu</name>
      <address>
        <city>Barcelona</city>
        <zip>08026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de las Nieves</name>
      <address>
        <city>Granada</city>
        <zip>18014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22.</citation>
    <PMID>20961243</PMID>
  </reference>
  <reference>
    <citation>Ussia GP, Scarabelli M, Mule M, Barbanti M, Sarkar K, Cammalleri V, Imme S, Aruta P, Pistritto AM, Gulino S, Deste W, Capodanno D, Tamburino C. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol. 2011 Dec 15;108(12):1772-6. doi: 10.1016/j.amjcard.2011.07.049. Epub 2011 Sep 10.</citation>
    <PMID>21907949</PMID>
  </reference>
  <reference>
    <citation>Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, Thourani VH, Babaliaros VC, Webb JG, Herrmann HC, Bavaria JE, Kodali S, Brown DL, Bowers B, Dewey TM, Svensson LG, Tuzcu M, Moses JW, Williams MR, Siegel RJ, Akin JJ, Anderson WN, Pocock S, Smith CR, Leon MB; PARTNER Trial Investigators. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012 May 3;366(18):1696-704. doi: 10.1056/NEJMoa1202277. Epub 2012 Mar 26. Erratum In: N Engl J Med. 2012 Aug 30;367(9):881.</citation>
    <PMID>22443478</PMID>
  </reference>
  <reference>
    <citation>Tousek P, Kocka V, Sulzenko J, Bednar F, Linkova H, Widimsky P. Pharmacodynamic effect of clopidogrel in patients undergoing transcatheter aortic valve implantation. Biomed Res Int. 2013;2013:386074. doi: 10.1155/2013/386074. Epub 2013 Jul 15.</citation>
    <PMID>23956980</PMID>
  </reference>
  <reference>
    <citation>Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011 Sep 6;124(10):1132-7. doi: 10.1161/CIRCULATIONAHA.111.029165. Epub 2011 Aug 29.</citation>
    <PMID>21875913</PMID>
  </reference>
  <reference>
    <citation>Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, Cannon CP, Heras M, Lopes RD, Morais J, Mahaffey KW, Bach RG, Wojdyla D, Wallentin L; PLATO study group. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):680-8. doi: 10.1161/CIRCOUTCOMES.111.964395.</citation>
    <PMID>22991347</PMID>
  </reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <last_update_submitted>August 1, 2018</last_update_submitted>
  <last_update_submitted_qc>August 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital de Meixoeiro</investigator_affiliation>
    <investigator_full_name>Andres Iñiguez Romo, MD, PhD</investigator_full_name>
    <investigator_title>Chief, Cardiology Department, Hospital Alvaro Cunqueiro</investigator_title>
  </responsible_party>
  <keyword>Aortic stenosis</keyword>
  <keyword>TAVI</keyword>
  <keyword>TAVR</keyword>
  <keyword>Transcatheter aortic valve implantation</keyword>
  <keyword>Ticagrelor</keyword>
  <keyword>Antiplatelet reactivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Valve Stenosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02224066
org study id: MEIX-VALV-002
secondary id: REAC TAVI
nct id: NCT02224066
lead sponsor: 
has dmc: Yes
A high platelet reactivity in patients with severe symptomatic Aortic Stenosis (AS) selected
      for TAVI (Transcatheter aortic valve implantation) procedure has been demonstrated
      previously, and the use of double antiaggregation therapy (DAPT) with Clopidogrel and
      Acetylsalicylic acid (ASA) do not achieve consistent and adequate suppression of platelet
      reactivity. The purpose of this study is evaluate the efficacy of ticagrelor alone versus
      DAPT with clopidogrel and aspirin for the suppression of high platelet reactivity following
      TAVI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by a system to verify the patient's platelet reactivity (VerifyNow P2Y12 assay).
time frame: Three months after antiplatelet treatment initiation following procedure.
measure: Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by VerifyNow P2Y12 assay.
time frame: Six hours after antiplatelet treatment initiation following procedure.
measure: Assess the safety of antiplatelet monotherapy with ticagrelor compared to DAPT with aspirin and clopidogrel, with regard to the incidence of investigator-reported clinical events according to predefined criteria, including bleeding definitions.
time frame: Three months after antiplatelet treatment initiation following procedure.
arm group label: Ticagrelor
arm group type: Experimental
description: Patients with high-on-treatment platelet reactivity (PRU ≥ 208)
arm group label: Aspirin/Clopidogrel
arm group type: Active Comparator
description: Patients with high-on-treatment platelet reactivity (PRU ≥ 208)
arm group label: Registry arm
arm group type: No Intervention
description: Patients with normal-on-treatment platelet reactivity (PRU < 208) will continue with Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI.
intervention type: Drug
intervention name: Ticagrelor 90 mg twice per day during three months following TAVI
arm group label: Ticagrelor
intervention type: Drug
intervention name: Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI
arm group label: Aspirin/Clopidogrel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrés Iñiguez Romo, MD;Phd
role: Principal Investigator
affiliation: Xerencia de Xestión Integrada de Vigo
last name: Victor A Jimenez Diaz, MD; Msc
role: Principal Investigator
affiliation: Xerencia de Xestión Integrada de Vigo
last name: Pablo Juan Salvadores, Pharma; MPH
role: Study Director
affiliation: Xerencia xestión integrada de Vigo
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
citation: Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22.
PMID: 20961243
citation: Ussia GP, Scarabelli M, Mule M, Barbanti M, Sarkar K, Cammalleri V, Imme S, Aruta P, Pistritto AM, Gulino S, Deste W, Capodanno D, Tamburino C. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol. 2011 Dec 15;108(12):1772-6. doi: 10.1016/j.amjcard.2011.07.049. Epub 2011 Sep 10.
PMID: 21907949
citation: Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, Thourani VH, Babaliaros VC, Webb JG, Herrmann HC, Bavaria JE, Kodali S, Brown DL, Bowers B, Dewey TM, Svensson LG, Tuzcu M, Moses JW, Williams MR, Siegel RJ, Akin JJ, Anderson WN, Pocock S, Smith CR, Leon MB; PARTNER Trial Investigators. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012 May 3;366(18):1696-704. doi: 10.1056/NEJMoa1202277. Epub 2012 Mar 26. Erratum In: N Engl J Med. 2012 Aug 30;367(9):881.
PMID: 22443478
citation: Tousek P, Kocka V, Sulzenko J, Bednar F, Linkova H, Widimsky P. Pharmacodynamic effect of clopidogrel in patients undergoing transcatheter aortic valve implantation. Biomed Res Int. 2013;2013:386074. doi: 10.1155/2013/386074. Epub 2013 Jul 15.
PMID: 23956980
citation: Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011 Sep 6;124(10):1132-7. doi: 10.1161/CIRCULATIONAHA.111.029165. Epub 2011 Aug 29.
PMID: 21875913
citation: Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, Cannon CP, Heras M, Lopes RD, Morais J, Mahaffey KW, Bach RG, Wojdyla D, Wallentin L; PLATO study group. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):680-8. doi: 10.1161/CIRCOUTCOMES.111.964395.
PMID: 22991347
responsible party type: Principal Investigator
investigator affiliation: Hospital de Meixoeiro
investigator full name: Andres Iñiguez Romo, MD, PhD
investigator title: Chief, Cardiology Department, Hospital Alvaro Cunqueiro
mesh term: Aortic Valve Stenosis
mesh term: Aspirin
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: Undecided