<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/NCT03001960</url>
  </required_header>
  <id_info>
    <org_study_id>DAPT-TAVI 01</org_study_id>
    <nct_id>NCT03001960</nct_id>
  </id_info>
  <brief_title>Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in TAVI</brief_title>
  <acronym>DAPT-TAVI</acronym>
  <official_title>Dual AntiPlatelet Therapies for Prevention of Periinterventional Embolic Events in Transcatheter Aortic Valve Implantation (TAVI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Prof. Dr. Jochen Fiebach, Center for Stroke Research Berlin (CSB), Charité - Universitaetsmedizin Berlin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      TAVI is increasingly adopted as standard treatment for many subgroups of patients with aortic&#xD;
      stenosis. However, due to a lack of data there is yet no TAVI-specific guidance regarding the&#xD;
      optimum periinterventional drug regimen.&#xD;
&#xD;
      The study evaluates the effect of dual antiplatelet pretreatment on periinterventional&#xD;
      embolic cerebral lesions and bleeding complications in patients undergoing transfemoral&#xD;
      aortic valve implantation (TF-TAVI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients undergoing TAVI bear a high risk of ischaemic stroke, which is an independent&#xD;
      predictor of mortality1. Dual antiplatelet therapy (DAPT) is recommended by current&#xD;
      guidelines without clear specifications on the time of initiation of treatment due to a lack&#xD;
      of data. While some centers initiate DAPT with aspirin and clopidogrel prior to TAVI to&#xD;
      reduce the rate of periinterventional embolic events, others start these medications after&#xD;
      the procedure.Data on antithrombotic therapy during TAVI are scarce and no randomized&#xD;
      evaluation has been performed to demonstrate what the best strategy is during the procedure.&#xD;
&#xD;
      Therefore, the objective of this clinical trial is to assess the efficacy of pre- versus&#xD;
      postoperative dual antiplatelet loading with Aspirin and Clopidogrel on volume of&#xD;
      periinterventional cerebral ischemic lesions as quantified by diffusion weight MRI (DW-MRI)&#xD;
      and neurocognitive function in patients undergoing transfemoral aortic valve replacement. The&#xD;
      statistical trial design assumes superiority of preloading with DAPT regarding the primary&#xD;
      endpoint.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>March 2017</start_date>
  <completion_date type="Anticipated">April 2018</completion_date>
  <primary_completion_date type="Anticipated">March 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total volume of new cerebral lesions on MRI after TAVI versus Baseline</measure>
    <time_frame>Total volume of new cerebral lesions on MRI, 24-72h after TAV versus Baseline</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>New lesion volume of cerebral embolization in patients treated with ASS and Clopidogrel before versus after TAVI</measure>
    <time_frame>24-72h post TAVI versus baseline</time_frame>
    <description>Total new lesion volume is defined as the sum volume of all new cerebral ischemic lesions on the post-procedural MRI relative to the pre-TAVR cerebral MRI scan (on diffusion weighted and FLAIR MRI images).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>location of new cerebral lesions early AFTER TAVI</measure>
    <time_frame>24-72h after TAVI</time_frame>
    <description>To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>extent of new cerebral lesions early AFTER TAVI</measure>
    <time_frame>24-72h after TAVI</time_frame>
    <description>To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of different neurocognitive tests before and after TAVI procedure</measure>
    <time_frame>24-72 h after TAVI</time_frame>
    <description>To evaluate neurologic function with a battery of neurocognitive tests and to correlate these findings to cerebral MRI scans</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of clinically apparent non-cerebral emboli after TAVI</measure>
    <time_frame>24-72 h after TAVI</time_frame>
    <description>To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>localization of clinically apparent non-cerebral emboli after TAVI</measure>
    <time_frame>24-72 h after TAVI</time_frame>
    <description>To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score.</measure>
    <time_frame>24-72 h after TAVI</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Aortic Valve Stenosis</condition>
  <condition>Transcatheter Aortic Valve Replacement</condition>
  <condition>Intracranial Embolism</condition>
  <arm_group>
    <arm_group_label>Group 1- PREloading BEFORE TAVI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aspirin 100 mg loading orally 6-12 hours before TAVI and&#xD;
Clopidogrel 600mg loading 6-12 before TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 - POSTLoading AFTER TAVI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aspirin 100 mg loading orally 6-12 hours after TAVI and&#xD;
Clopidogrel 600mg loading 6-12 hours after TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Preloading before TAVI</intervention_name>
    <description>Preloading with Aspirin and Clopidogrel before TAVI</description>
    <arm_group_label>Group 1- PREloading BEFORE TAVI</arm_group_label>
    <other_name>ASS, Plavix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Postloading after TAVI</intervention_name>
    <description>Postloading with Aspirin and Clopidogrel after TAVI</description>
    <arm_group_label>Group 2 - POSTLoading AFTER TAVI</arm_group_label>
    <other_name>ASS, Plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients &gt;18 years and &lt;90 years&#xD;
&#xD;
          -  Patients undergoing TF-TAVI for severe aortic stenosis (combined with aortic&#xD;
             regurgitation)&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  TIA/Stroke within last 90 days&#xD;
&#xD;
          -  Aortic valve-in-valve procedures&#xD;
&#xD;
          -  TAVI for treatment of isolated aortic regurgitation&#xD;
&#xD;
          -  known significant carotid stenosis (&gt;70%)&#xD;
&#xD;
          -  Prior myocardial infarction or revascularization with PCI or CABG within past 3 months&#xD;
&#xD;
          -  Clopidogrel and/ or Aspirin within past 7 days&#xD;
&#xD;
          -  any other indication for (dual) antiplatelet therapy&#xD;
&#xD;
          -  Contraindication to MRI (MRI conditional pacemakers accepted!)&#xD;
&#xD;
          -  participation in another interventional trial&#xD;
&#xD;
          -  cardiogenic shock (positive shock index OR need for catecholamine support OR systolic&#xD;
             bloodpressure &lt; 90 mmHg) or need for pre-hospital intubation&#xD;
&#xD;
          -  cardiac arrest &lt;90 days prior to randomization&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O'Brien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM, Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT Registry. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA. 2015 Mar 10;313(10):1019-28. doi: 10.1001/jama.2015.1474.</citation>
    <PMID>25756438</PMID>
  </reference>
  <reference>
    <citation>Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, Bogers AJ, Piazza N, Kappetein AP. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013 Sep 10;62(11):1002-12. doi: 10.1016/j.jacc.2013.05.015. Epub 2013 May 30.</citation>
    <PMID>23727214</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>December 27, 2016</last_update_submitted>
  <last_update_submitted_qc>December 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Alexander Lauten</investigator_full_name>
    <investigator_title>Prof. Dr. med.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intracranial Embolism</mesh_term>
    <mesh_term>Embolism</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clopidogrel</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03001960
org study id: DAPT-TAVI 01
nct id: NCT03001960
lead sponsor: 
collaborator: 
has dmc: No
TAVI is increasingly adopted as standard treatment for many subgroups of patients with aortic
      stenosis. However, due to a lack of data there is yet no TAVI-specific guidance regarding the
      optimum periinterventional drug regimen.

      The study evaluates the effect of dual antiplatelet pretreatment on periinterventional
      embolic cerebral lesions and bleeding complications in patients undergoing transfemoral
      aortic valve implantation (TF-TAVI).
Patients undergoing TAVI bear a high risk of ischaemic stroke, which is an independent
      predictor of mortality1. Dual antiplatelet therapy (DAPT) is recommended by current
      guidelines without clear specifications on the time of initiation of treatment due to a lack
      of data. While some centers initiate DAPT with aspirin and clopidogrel prior to TAVI to
      reduce the rate of periinterventional embolic events, others start these medications after
      the procedure.Data on antithrombotic therapy during TAVI are scarce and no randomized
      evaluation has been performed to demonstrate what the best strategy is during the procedure.

      Therefore, the objective of this clinical trial is to assess the efficacy of pre- versus
      postoperative dual antiplatelet loading with Aspirin and Clopidogrel on volume of
      periinterventional cerebral ischemic lesions as quantified by diffusion weight MRI (DW-MRI)
      and neurocognitive function in patients undergoing transfemoral aortic valve replacement. The
      statistical trial design assumes superiority of preloading with DAPT regarding the primary
      endpoint.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Total volume of new cerebral lesions on MRI after TAVI versus Baseline
time frame: Total volume of new cerebral lesions on MRI, 24-72h after TAV versus Baseline
measure: New lesion volume of cerebral embolization in patients treated with ASS and Clopidogrel before versus after TAVI
time frame: 24-72h post TAVI versus baseline
description: Total new lesion volume is defined as the sum volume of all new cerebral ischemic lesions on the post-procedural MRI relative to the pre-TAVR cerebral MRI scan (on diffusion weighted and FLAIR MRI images).
measure: location of new cerebral lesions early AFTER TAVI
time frame: 24-72h after TAVI
description: To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan
measure: extent of new cerebral lesions early AFTER TAVI
time frame: 24-72h after TAVI
description: To evaluate cerebral embolisation, which is not procedure related, cerebral embolisation on MRI will be before TAVI versus the post-TAVI MRI scan
measure: Assessment of different neurocognitive tests before and after TAVI procedure
time frame: 24-72 h after TAVI
description: To evaluate neurologic function with a battery of neurocognitive tests and to correlate these findings to cerebral MRI scans
measure: Extent of clinically apparent non-cerebral emboli after TAVI
time frame: 24-72 h after TAVI
description: To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...)
measure: localization of clinically apparent non-cerebral emboli after TAVI
time frame: 24-72 h after TAVI
description: To describe extent and localization of non-cerebral embolisation (e.g. pulmonary embolism, limb ischaemia...)
measure: Evaluation of possible changes in quality of life after TAVI with EQ-5D questionnaire sum score.
time frame: 24-72 h after TAVI
arm group label: Group 1- PREloading BEFORE TAVI
arm group type: Experimental
description: Aspirin 100 mg loading orally 6-12 hours before TAVI and
Clopidogrel 600mg loading 6-12 before TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day
arm group label: Group 2 - POSTLoading AFTER TAVI
arm group type: Experimental
description: Aspirin 100 mg loading orally 6-12 hours after TAVI and
Clopidogrel 600mg loading 6-12 hours after TAVI followed by maintenance dose of 100mg aspirin and 75mg clopidogrel per day
intervention type: Drug
intervention name: Preloading before TAVI
description: Preloading with Aspirin and Clopidogrel before TAVI
arm group label: Group 1- PREloading BEFORE TAVI
other name: ASS, Plavix
intervention type: Drug
intervention name: Postloading after TAVI
description: Postloading with Aspirin and Clopidogrel after TAVI
arm group label: Group 2 - POSTLoading AFTER TAVI
other name: ASS, Plavix
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
citation: Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O'Brien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM, Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT Registry. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA. 2015 Mar 10;313(10):1019-28. doi: 10.1001/jama.2015.1474.
PMID: 25756438
citation: Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, Bogers AJ, Piazza N, Kappetein AP. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013 Sep 10;62(11):1002-12. doi: 10.1016/j.jacc.2013.05.015. Epub 2013 May 30.
PMID: 23727214
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Alexander Lauten
investigator title: Prof. Dr. med.
mesh term: Intracranial Embolism
mesh term: Embolism
mesh term: Aortic Valve Stenosis
mesh term: Clopidogrel