<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/NCT04417634</url>
  </required_header>
  <id_info>
    <org_study_id>2020-1</org_study_id>
    <nct_id>NCT04417634</nct_id>
  </id_info>
  <brief_title>RFR and FFR for the the Prediction of Post-PCI Results</brief_title>
  <acronym>PICIO</acronym>
  <official_title>Pullback wIth Resting Full-Cycle Flow ratIO or Fractional Flow Reserve for the Prediction of Post-PCI Hemodynamic Outcomes. A Study in Patients With Diffuse Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johannes Gutenberg University Mainz</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to record hemodynamic pullback information using continuous resting&#xD;
      full-cycle flow ratio (RFR) and fractional flow reserve (FFR) in patients with diffuse&#xD;
      coronary artery disease. The capacity of the two indexes to predict the hemodynamic outcome&#xD;
      after stenting will be compared.&#xD;
&#xD;
      Goals of the study are:&#xD;
&#xD;
        -  To study the accuracy of RFR/FFR gradients in predicting the change in whole-vessel&#xD;
           RFR/FFR after PCI.&#xD;
&#xD;
        -  To identify a threshold in the RFR/FFR gradient that is predictive of pathological&#xD;
           RFR/FFR also after the PCI of the first lesion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study of the hemodynamic relevance of coronary stenoses is a well-validated method to&#xD;
      identify coronary lesions to be treated. A number of studies show that FFR-guided PCI is&#xD;
      superior to angiography guided PCI2-4. The achievement of maximal hyperemia is a prerequisite&#xD;
      for FFR measurements. Hyperemia is usually achieved with the intravenous or intracoronary&#xD;
      infusion of adenosine, which requires time and is potentially associated with discomfort for&#xD;
      the patient. To avoid this, resting indexes have been developed. The instantaneous flow&#xD;
      reserve (iFr) was the first of these indexes, and two large studies have shown that this&#xD;
      parameter is non-inferior to FFR in terms of patient prognosis5. More recently, a number of&#xD;
      other parameters have been developed, among which the RFR (resting flow ratio), which can be&#xD;
      measured with the same intracoronary wire as the FFR and therefore requires no additional&#xD;
      procedures. Studies show that these methods are equivalent6. The advantage of these resting&#xD;
      indexes (which are all included in the most recent AHA/ACC guidelines7, 8), is that they do&#xD;
      not require hyperemia. This might represent a particular advantage in the setting of tandem&#xD;
      stenoses or diffuse disease. Since hyperemic flow in a vessel is limited by each one of the&#xD;
      stenoses present in that vessel, each individual stenosis limits the capacity of FFR to&#xD;
      assess the hemodynamic relevance of the other ones. In other words, invasive measurements of&#xD;
      coronary hemodynamics using FFR in the setting of diffuse or tandem lesions are complicated&#xD;
      by the fact that maximal hyperemia cannot be achieved, which limits the capacity of FFR to&#xD;
      assess the hemodynamic relevance of individual focal stenoses. In this setting, the usual&#xD;
      binary system (FFR &lt; or &gt; 0.80) cannot be easily applied.&#xD;
&#xD;
      This limitation is independent of the sequence of the stenoses: proximal lesions limit the&#xD;
      reliability of FFR measurements in distal stenoses and vice versa (as long as no significant&#xD;
      side branches are present between the two lesions). Since hyperemic flow declines&#xD;
      significantly as soon as a 50% reduction in lumen diameter is present, even apparently&#xD;
      non-relevant lesions may compromise any assessment based on hyperemia. This phenomenon,&#xD;
      called hemodynamic interdependence of stenoses under conditions of hyperemia represents a&#xD;
      significant limitation that applies to FFR but not to hyperemia-free indexes.&#xD;
&#xD;
      In order to address this issue in routine practice, FFR is measured first, then a pullback is&#xD;
      performed and the lesion/segment where the pullback identifies the highest gradient is&#xD;
      treated first. The removal of this stenosis increases maximal achievable hyperemic flow, thus&#xD;
      increasing the significance of the remaining lesions. FFR is then measured again to test the&#xD;
      hemodynamic significance of the other stenoses at a higher level of hyperemia. The capacity&#xD;
      of FFR to predict whether removal of the first stenosis will be associated with the&#xD;
      normalization of FFR is very limited, which requires that FFR be measured multiple times,&#xD;
      prolonging the procedure and increasing the discomfort for the patient.&#xD;
&#xD;
      When studying coronary stenoses, the advantage of resting hemodynamic indexes is that&#xD;
      non-critical stenoses (ie below 90%) do not modify resting blood flow. Because resting flow&#xD;
      is more constant, and the effect of PCI is minimal, resting pressure changes measured across&#xD;
      sequential lesions are likely to be more predictable.The hypothesis of the study is that, as&#xD;
      compared to FFR, RFR will provide a better estimate of post-PCI hemodynamic outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 10, 2020</start_date>
  <completion_date type="Anticipated">June 10, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 10, 2024</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>
    <intervention_model_description>The study is a single-center, randomized superiority trial to compare two strategies for the assessment of the hemodynamic relevance of coronary lesions.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute difference between RFR observed and expected as compared to FFR observed versus expected.</measure>
    <time_frame>1 day</time_frame>
    <description>Comparison of |RFRexp-RFRobs| vs. |FFRexp-FFRobs| (i.e., absolute differences between expected and observed final hemodynamic result) RFRexp and FFRexp are defined as (RFRbas plus RFRGrad) and (FFRbas plus FFRGrad)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>RFR: resting full-cycle ratio</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RFR will be used to drive PCI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FFR: fractional flow reserve</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>FFR will be used to drive PCI</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>RFR</intervention_name>
    <description>Measurement of resting flow ratio</description>
    <arm_group_label>RFR: resting full-cycle ratio</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>FFR</intervention_name>
    <description>Measurement of fractional flow reserve</description>
    <arm_group_label>FFR: fractional flow reserve</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must meet ALL of the inclusion criteria:&#xD;
&#xD;
               -  Clinical indication for elective percutaneous coronary intervention of a stenosis&#xD;
                  &gt;40% and &lt;90% with clinical indication to percutaneous intervention (PCI)&#xD;
                  requiring functional assessment. Note: the decision to perform functional&#xD;
                  assessment will have to be taken before, and independently of, the inclusion and&#xD;
                  randomization in the study.&#xD;
&#xD;
               -  Documented heart team (when applicable, as per guidelines) decision for&#xD;
                  revascularization via PCI&#xD;
&#xD;
               -  Patient ≥18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients will be excluded if ANY of the exclusion criteria is met:&#xD;
&#xD;
               -  Cardiogenic shock&#xD;
&#xD;
               -  Any contraindication to PCI according to guidelines&#xD;
&#xD;
               -  Presence of a coronary artery bypass grafting (CABG) in the territory under study&#xD;
&#xD;
               -  Culprit vessels in patients with ST-segment elevation myocardial infarction&#xD;
                  (STEMI)&#xD;
&#xD;
               -  TIMI (Thrombolysis in Myocardial Infarction) flow grade &lt; 3&#xD;
&#xD;
               -  Lesion severity &gt; 90% by visual assessment&#xD;
&#xD;
               -  Presence of thrombus&#xD;
&#xD;
               -  Participation in another randomized interventional study&#xD;
&#xD;
               -  Patient unable to give informed consent&#xD;
&#xD;
               -  Women of child-bearing potential or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Tommaso Gori</last_name>
    <phone>+491721052846</phone>
    <email>tomgori@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Center of Cardiology, Cardiology I, university hospital Mainz</name>
      <address>
        <city>Mainz</city>
        <state>Rheinland-Pfalz</state>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tommaso Gori, Prof Dr, PhD</last_name>
      <phone>+49 (0) 6131 17 2729</phone>
      <email>tommaso.gori@unimedizin-mainz.de</email>
    </contact>
    <investigator>
      <last_name>Tommaso Gori, Prof Dr, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johannes Gutenberg University Mainz</investigator_affiliation>
    <investigator_full_name>Tommaso Gori</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>stent</keyword>
  <keyword>coronary stenosis</keyword>
  <keyword>Angina</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04417634
org study id: 2020-1
nct id: NCT04417634
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of this study is to record hemodynamic pullback information using continuous resting
      full-cycle flow ratio (RFR) and fractional flow reserve (FFR) in patients with diffuse
      coronary artery disease. The capacity of the two indexes to predict the hemodynamic outcome
      after stenting will be compared.

      Goals of the study are:

        -  To study the accuracy of RFR/FFR gradients in predicting the change in whole-vessel
           RFR/FFR after PCI.

        -  To identify a threshold in the RFR/FFR gradient that is predictive of pathological
           RFR/FFR also after the PCI of the first lesion.
The study of the hemodynamic relevance of coronary stenoses is a well-validated method to
      identify coronary lesions to be treated. A number of studies show that FFR-guided PCI is
      superior to angiography guided PCI2-4. The achievement of maximal hyperemia is a prerequisite
      for FFR measurements. Hyperemia is usually achieved with the intravenous or intracoronary
      infusion of adenosine, which requires time and is potentially associated with discomfort for
      the patient. To avoid this, resting indexes have been developed. The instantaneous flow
      reserve (iFr) was the first of these indexes, and two large studies have shown that this
      parameter is non-inferior to FFR in terms of patient prognosis5. More recently, a number of
      other parameters have been developed, among which the RFR (resting flow ratio), which can be
      measured with the same intracoronary wire as the FFR and therefore requires no additional
      procedures. Studies show that these methods are equivalent6. The advantage of these resting
      indexes (which are all included in the most recent AHA/ACC guidelines7, 8), is that they do
      not require hyperemia. This might represent a particular advantage in the setting of tandem
      stenoses or diffuse disease. Since hyperemic flow in a vessel is limited by each one of the
      stenoses present in that vessel, each individual stenosis limits the capacity of FFR to
      assess the hemodynamic relevance of the other ones. In other words, invasive measurements of
      coronary hemodynamics using FFR in the setting of diffuse or tandem lesions are complicated
      by the fact that maximal hyperemia cannot be achieved, which limits the capacity of FFR to
      assess the hemodynamic relevance of individual focal stenoses. In this setting, the usual
      binary system (FFR < or > 0.80) cannot be easily applied.

      This limitation is independent of the sequence of the stenoses: proximal lesions limit the
      reliability of FFR measurements in distal stenoses and vice versa (as long as no significant
      side branches are present between the two lesions). Since hyperemic flow declines
      significantly as soon as a 50% reduction in lumen diameter is present, even apparently
      non-relevant lesions may compromise any assessment based on hyperemia. This phenomenon,
      called hemodynamic interdependence of stenoses under conditions of hyperemia represents a
      significant limitation that applies to FFR but not to hyperemia-free indexes.

      In order to address this issue in routine practice, FFR is measured first, then a pullback is
      performed and the lesion/segment where the pullback identifies the highest gradient is
      treated first. The removal of this stenosis increases maximal achievable hyperemic flow, thus
      increasing the significance of the remaining lesions. FFR is then measured again to test the
      hemodynamic significance of the other stenoses at a higher level of hyperemia. The capacity
      of FFR to predict whether removal of the first stenosis will be associated with the
      normalization of FFR is very limited, which requires that FFR be measured multiple times,
      prolonging the procedure and increasing the discomfort for the patient.

      When studying coronary stenoses, the advantage of resting hemodynamic indexes is that
      non-critical stenoses (ie below 90%) do not modify resting blood flow. Because resting flow
      is more constant, and the effect of PCI is minimal, resting pressure changes measured across
      sequential lesions are likely to be more predictable.The hypothesis of the study is that, as
      compared to FFR, RFR will provide a better estimate of post-PCI hemodynamic outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is a single-center, randomized superiority trial to compare two strategies for the assessment of the hemodynamic relevance of coronary lesions.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Absolute difference between RFR observed and expected as compared to FFR observed versus expected.
time frame: 1 day
description: Comparison of |RFRexp-RFRobs| vs. |FFRexp-FFRobs| (i.e., absolute differences between expected and observed final hemodynamic result) RFRexp and FFRexp are defined as (RFRbas plus RFRGrad) and (FFRbas plus FFRGrad)
arm group label: RFR: resting full-cycle ratio
arm group type: Experimental
description: RFR will be used to drive PCI
arm group label: FFR: fractional flow reserve
arm group type: Active Comparator
description: FFR will be used to drive PCI
intervention type: Diagnostic Test
intervention name: RFR
description: Measurement of resting flow ratio
arm group label: RFR: resting full-cycle ratio
intervention type: Diagnostic Test
intervention name: FFR
description: Measurement of fractional flow reserve
arm group label: FFR: fractional flow reserve
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Tommaso Gori
phone: +491721052846
email: tomgori@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Johannes Gutenberg University Mainz
investigator full name: Tommaso Gori
investigator title: Clinical Professor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
sharing ipd: No