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/NCT05994729</url>
    </required_header>
    <id_info>
      <org_study_id>AH Card. 08-23</org_study_id>
      <nct_id>NCT05994729</nct_id>
    </id_info>
    <brief_title>IMPact of REnal Denervation in Patients With Coronary microvaScular dySfunctION: Study Design and Rationale</brief_title>
    <acronym>IMPRESSION</acronym>
    <official_title>IMPact of REnal Denervation in Patients With Coronary microvaScular dySfunctION: Study Design and Rationale</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aurelia Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aurelia 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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Long-standing hypertension may cause an impairment in microvascular coronary circulation&#xD;
        which is involved in many different cardiac conditions. Renal denervation (RDN) has been&#xD;
        successfully proven as a valuable and powerful therapeutic choice to consider for patients&#xD;
        with resistant hypertension; moreover this procedure looks promising in other cardiac disease&#xD;
        such as heart failure and atrial fibrillation, given its ability to downregulate sympathetic&#xD;
        nervous system The aim of this study is to explore the effect of renal denervation and blood&#xD;
        pressure control on coronary microvascular dysfunction.&#xD;
  &#xD;
        This is a multicenter, prospective, non randomized, open-label, interventional study.&#xD;
        Consecutive patients with resistant hypertension, non obstructive coronary artery disease and&#xD;
        documented microvascular dysfunction will be enrolled. Patients will undergo renal&#xD;
        denervation by Spyral Symplicity 3 and re-assessment of coronary microvascular function 6&#xD;
        months after the procedure. Primary endpoint will be the difference in average index of&#xD;
        microcirculatory resistance value.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The aim of this study is to evaluate the effect of radiofrequency RDN performed with Spyral&#xD;
        Symplicity 3 on microvascular function in patients with ascertained hypertension related&#xD;
        coronary microvascular dysfunction (hy-CMD) and/or hypertensive cardiomyopathy. Our&#xD;
        hypothesis is that RDN could improve invasive parameters of microvascular function in&#xD;
        patients with hy-CMD; these would mean that RDN would be able to at least partially revert&#xD;
        the pathogenesis of hy-CMD.&#xD;
  &#xD;
        The study design comprises an initial rule-in and enrollment phase, required to properly&#xD;
        select the target population, followed by the actual study procedural phase.&#xD;
  &#xD;
        Patients amenable to RDN will be hospitalized and enter the rule-in phase to check for&#xD;
        eligibility.&#xD;
  &#xD;
        Before performing the actual RDN, patients will be asked for the written informed consent to&#xD;
        receive physiological evaluation.&#xD;
  &#xD;
        Only patients that will be diagnosed with hy-CMD will eventually enter the actual study&#xD;
        phase.&#xD;
  &#xD;
        This phase will comprise repeated outpatients visits, according to a predetermined schedule,&#xD;
        including a new hospitalization at 6 months to reassess coronary microvascular physiology.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>IMR</measure>
      <time_frame>6 months</time_frame>
      <description>Matched comparison of IMR from baseline to 6 months after RDN</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>CFR</measure>
      <time_frame>6 months</time_frame>
      <description>Matched comparison of CFR from baseline to 6 months after RDN</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tmn</measure>
      <time_frame>6 months</time_frame>
      <description>Matched comparison of both resting and hyperemic TMN from baseline to 6 months after RDN</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systolic BP on APBM</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diastolic BP on ABPM</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average BP on ABPM</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Average Mean Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time in Therapeutic BP Range</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of total time spent with both systolic and diastolic BP within normality range measured on 24 hour Ambulatory Blood Pressure Monitoring</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>BP Medication Burden</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Total Number of BP medication prescribed to the subject</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mini-SAQ</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Average Score on Mini Seattle Angina Questionnaire (SAQ)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MACE</measure>
      <time_frame>6 Months</time_frame>
      <description>Percentage of patients experiencing a Major Adverse Cardiovascular Event</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NTproBNP</measure>
      <time_frame>6 Months</time_frame>
      <description>Matched Comparison of Average NTproBNP</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">87</enrollment>
    <condition>Coronary Microvascular Dysfunction</condition>
    <condition>Resistant Hypertension</condition>
    <condition>Hypertensive Heart Disease</condition>
    <arm_group>
      <arm_group_label>Candidates to RDN with ascertained CMD</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients that are candidates to receive RDN for resistant/difficult to control hypertension, who also have documented coronary microvascular dysfunction</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Invasive Physiological Assessment of Coronary Circulation</intervention_name>
      <description>After 2 months long rule-in phase required to exclude the unsuitable patients, study population will undergo RDN as indicated to treat resistant or difficult to control hypertension; 6 months after RDN, they will undergo invasive physiological study, comprehensive of Coronary Flow Reserve, Index of Microvascular Resistance, Mean Transit Time. These data will be then compared to the baseline ones obtained during the screening phase.</description>
      <arm_group_label>Candidates to RDN with ascertained CMD</arm_group_label>
      <other_name>CFR</other_name>
      <other_name>IMR</other_name>
      <other_name>Tmn</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Rul-in Phase Inclusion Criteria:&#xD;
  &#xD;
            -  Non obstructive stable coronary artery disease (CAD) on invasive coronary angiography&#xD;
               (defined as the absence of either &gt;50% angiographic stenosis or any flow limiting&#xD;
               lesion on functional evaluation)&#xD;
  &#xD;
            -  Suspected diagnosis of difficult to control/ resistant hypertension for which renal&#xD;
               denervation by radiofrequency ablation with Spyral Symplicity 3 could be considered.&#xD;
  &#xD;
          Rule-in Phase Exclusion Criteria:&#xD;
  &#xD;
            -  Initiation of either nitrates, beta-blocker or calcium channel blocker less than 30&#xD;
               days before the end of the rule-in phase&#xD;
  &#xD;
            -  Physiological assessment performed during first medical contact documenting preserved&#xD;
               coronary microvascular function&#xD;
  &#xD;
            -  Physiological assessment performed at the &quot;first contact&quot; hospitalization followed by&#xD;
               modification of medical therapy during the rule-in phase, before RDN&#xD;
  &#xD;
            -  Acceptable blood pressure control after medical treatment optimization&#xD;
  &#xD;
            -  Identification of secondary causes of hypertension&#xD;
  &#xD;
            -  Renal artery anatomy not suitable for RDN&#xD;
  &#xD;
            -  Ejection fraction below 30%&#xD;
  &#xD;
            -  Life expectancy below 1 year&#xD;
  &#xD;
            -  Indication to cardiac surgery&#xD;
  &#xD;
            -  Adenosine allergy&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Large necrotic area documented by either MRI, SPECT or combination of ECG signs +&#xD;
               Echocardiographic images.&#xD;
  &#xD;
            -  Hemodynamic instability&#xD;
  &#xD;
            -  Refuse to sign informed consent&#xD;
  &#xD;
            -  Age below 18 or above 80&#xD;
  &#xD;
          Study Phase Inclusion Criteria:&#xD;
  &#xD;
            -  Having coronary microvascular dysfunction documented by invasive functional assessment&#xD;
               (IMR&gt;25 and or CFR &lt; 2)&#xD;
  &#xD;
            -  Fulfilling all the rule-in phase inclusion criteria without any rule-in phase&#xD;
               exclusion criteria&#xD;
  &#xD;
          Study Phase Exclusion Criteria:&#xD;
  &#xD;
            -  Refuse to sign informed consent&#xD;
  &#xD;
            -  Evidence of newly detected obstructive CAD on invasive coronary angiography performed&#xD;
               6 months after RDN&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fabrizio Tomai, MD, FACC, FESC</last_name>
      <role>Principal Investigator</role>
      <affiliation>Aurelia Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>stefano migliaro, MD</last_name>
      <role>Study Chair</role>
      <affiliation>Aurelia Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Fabrizio Tomai, MD, FACC, FESC</last_name>
      <phone>0039 06 65975725</phone>
      <email>fabriziotomai@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>stefano migliaro, MD</last_name>
      <phone>0039 3453373825</phone>
      <email>migliaro.stefano@gmail.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 9, 2023</last_update_submitted>
    <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>MVD</keyword>
    <keyword>HHD</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Heart Diseases</mesh_term>
    </condition_browse>
    <!-- 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/NCT05994729
  org study id: AH Card. 08-23
  nct id: NCT05994729
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Long-standing hypertension may cause an impairment in microvascular coronary circulation
        which is involved in many different cardiac conditions. Renal denervation (RDN) has been
        successfully proven as a valuable and powerful therapeutic choice to consider for patients
        with resistant hypertension; moreover this procedure looks promising in other cardiac disease
        such as heart failure and atrial fibrillation, given its ability to downregulate sympathetic
        nervous system The aim of this study is to explore the effect of renal denervation and blood
        pressure control on coronary microvascular dysfunction.
  
        This is a multicenter, prospective, non randomized, open-label, interventional study.
        Consecutive patients with resistant hypertension, non obstructive coronary artery disease and
        documented microvascular dysfunction will be enrolled. Patients will undergo renal
        denervation by Spyral Symplicity 3 and re-assessment of coronary microvascular function 6
        months after the procedure. Primary endpoint will be the difference in average index of
        microcirculatory resistance value.
  The aim of this study is to evaluate the effect of radiofrequency RDN performed with Spyral
        Symplicity 3 on microvascular function in patients with ascertained hypertension related
        coronary microvascular dysfunction (hy-CMD) and/or hypertensive cardiomyopathy. Our
        hypothesis is that RDN could improve invasive parameters of microvascular function in
        patients with hy-CMD; these would mean that RDN would be able to at least partially revert
        the pathogenesis of hy-CMD.
  
        The study design comprises an initial rule-in and enrollment phase, required to properly
        select the target population, followed by the actual study procedural phase.
  
        Patients amenable to RDN will be hospitalized and enter the rule-in phase to check for
        eligibility.
  
        Before performing the actual RDN, patients will be asked for the written informed consent to
        receive physiological evaluation.
  
        Only patients that will be diagnosed with hy-CMD will eventually enter the actual study
        phase.
  
        This phase will comprise repeated outpatients visits, according to a predetermined schedule,
        including a new hospitalization at 6 months to reassess coronary microvascular physiology.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: IMR
  time frame: 6 months
  description: Matched comparison of IMR from baseline to 6 months after RDN
  measure: CFR
  time frame: 6 months
  description: Matched comparison of CFR from baseline to 6 months after RDN
  measure: Tmn
  time frame: 6 months
  description: Matched comparison of both resting and hyperemic TMN from baseline to 6 months after RDN
  measure: Systolic BP on APBM
  time frame: 6 Months
  description: Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring
  measure: Diastolic BP on ABPM
  time frame: 6 Months
  description: Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring
  measure: Average BP on ABPM
  time frame: 6 Months
  description: Matched Comparison of Average Mean Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring
  measure: Time in Therapeutic BP Range
  time frame: 6 Months
  description: Matched Comparison of total time spent with both systolic and diastolic BP within normality range measured on 24 hour Ambulatory Blood Pressure Monitoring
  measure: BP Medication Burden
  time frame: 6 Months
  description: Matched Comparison of Total Number of BP medication prescribed to the subject
  measure: Mini-SAQ
  time frame: 6 Months
  description: Matched Comparison of Average Score on Mini Seattle Angina Questionnaire (SAQ)
  measure: MACE
  time frame: 6 Months
  description: Percentage of patients experiencing a Major Adverse Cardiovascular Event
  measure: NTproBNP
  time frame: 6 Months
  description: Matched Comparison of Average NTproBNP
  arm group label: Candidates to RDN with ascertained CMD
  arm group type: Experimental
  description: Patients that are candidates to receive RDN for resistant/difficult to control hypertension, who also have documented coronary microvascular dysfunction
  intervention type: Diagnostic Test
  intervention name: Invasive Physiological Assessment of Coronary Circulation
  description: After 2 months long rule-in phase required to exclude the unsuitable patients, study population will undergo RDN as indicated to treat resistant or difficult to control hypertension; 6 months after RDN, they will undergo invasive physiological study, comprehensive of Coronary Flow Reserve, Index of Microvascular Resistance, Mean Transit Time. These data will be then compared to the baseline ones obtained during the screening phase.
  arm group label: Candidates to RDN with ascertained CMD
  other name: CFR
  other name: IMR
  other name: Tmn
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Fabrizio Tomai, MD, FACC, FESC
  role: Principal Investigator
  affiliation: Aurelia Hospital
  last name: stefano migliaro, MD
  role: Study Chair
  affiliation: Aurelia Hospital
  last name: Fabrizio Tomai, MD, FACC, FESC
  phone: 0039 06 65975725
  email: fabriziotomai@gmail.com
  last name: stefano migliaro, MD
  phone: 0039 3453373825
  email: migliaro.stefano@gmail.com
  responsible party type: Sponsor
  mesh term: Heart Diseases