<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/NCT03246568</url>
  </required_header>
  <id_info>
    <org_study_id>CUHK-CARD-2017-RND</org_study_id>
    <nct_id>NCT03246568</nct_id>
  </id_info>
  <brief_title>Renal Nerve Denervation After Pulmonary Vein Isolation for Persistent Atrial Fibrillation</brief_title>
  <official_title>Renal Artery Sympathetic Denervation by Catheter Ablation After Pulmonary Vein Isolation for Persistent Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</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>
      Atrial fibrillation (AF) is the most common arrhythmia and it is associated with significant&#xD;
      morbidity and mortality. Electrical isolation of the pulmonary vein (PVI) by radiofrequency&#xD;
      energy or cryoablation has been shown to be an effective treatment of AF by reducing&#xD;
      morbidity, improving quality of life and functional capacity.&#xD;
&#xD;
      Renal artery sympathetic denervation (RND) by catheter ablation has been shown in a&#xD;
      preliminary study to improve outcome of PVI in patients with paroxysmal and/or persistent AF&#xD;
      with concomitant refractory or moderate hypertension. In patients with renal impairment, RND&#xD;
      also conferred benefit in reducing AF recurrence after PVI. The initial indication for&#xD;
      catheter-based RND is for blood pressure control in patients with resistant hypertension.&#xD;
      However, a recent study failed to show significant difference in blood pressure reduction by&#xD;
      RND. Therefore, the effect of RND on AF suppression may be independent of blood pressure&#xD;
      control. Possible mechanisms of RND on AF may include risk factors modification and&#xD;
      anti-arrhythmic effect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective randomized study aimed to evaluate the effect of RDN added to PVI for&#xD;
      persistent AF. Study will be performed in accordance with Declaration of Helsinki.&#xD;
&#xD;
      Study Hypothesis: Catheter based RDN can prevent recurrence of AF in patient with persistent&#xD;
      AF undergoing PVI by mechanism not related to hypertension control.&#xD;
&#xD;
      Primary outcome measure: Freedom from documented AF episodes post PVI as defined by longer&#xD;
      than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure&#xD;
      with or without antiarrhythmic medication.&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      This is an exploratory study, the sample size calculation will not be applied and arbitrary&#xD;
      assign 20 subjects to each arm will be adopted.&#xD;
&#xD;
      Randomization Arms:&#xD;
&#xD;
      Patients are randomized in 1:1 fraction to one of the following arms:&#xD;
&#xD;
        1. PVI by cryo-balloon ablation without linear ablation;&#xD;
&#xD;
        2. PVI by cryo-balloon ablation without linear ablation plus bilateral RND using a&#xD;
           multi-electrode renal denervation catheter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    no funding to purchase study device&#xD;
  </why_stopped>
  <start_date type="Actual">September 17, 2018</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 2020</primary_completion_date>
  <phase>N/A</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>Research on the Basis of Earlier Theory Renal artery sympathetic denervation (RND) by catheter ablation has been shown in a preliminary study to improve outcome of electrical isolation of the pulmonary vein (PVI) in patients with paroxysmal and/or persistent AF with concomitant refractory hypertension and the same group later showed renal sympathetic denervation improved outcome of PVI in the cohort of paroxysmal and/or persistent AF patients with moderate hypertension. In patients with renal impairment, RND also conferred benefit in reducing AF recurrence after PVI.The initial indication for catheter-based RND is for blood pressure control in patients with resistant hypertension. Early data from clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Freedom from documented AF episodes post PVI by implantable loop recorder by implantable loop recorder.</measure>
    <time_frame>2 to 18 months after procedure</time_frame>
    <description>Freedom from documented AF episodes post PVI as defined by longer than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Freedom from documented atrial arrhythmia episodes post PVI by implantable loop recorder.</measure>
    <time_frame>2 to 18 months after procedure</time_frame>
    <description>Freedom from documented atrial arrhythmia episodes post PVI as defined by longer than 30 seconds of atrial arrhythmia recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from symptomatic AF episodes post PVI by implantable loop recorder.</measure>
    <time_frame>2 to 18 months after procedure</time_frame>
    <description>Freedom from symptomatic AF episodes post PVI as defined by longer than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from symptomatic atrial arrhythmia episodes post PVI by implantable loop recorder.</measure>
    <time_frame>2 to 18 months after procedure</time_frame>
    <description>Freedom from symptomatic atrial arrhythmia episodes post PVI as defined by longer than 30 seconds of atrial arrhythmia recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from documented AF episodes post PVI by hand-held smartphone device.</measure>
    <time_frame>2 to 18 months after procedure</time_frame>
    <description>Freedom from documented AF episodes post PVI as defined by 30 seconds of AF recorded by hand-held smartphone device (i.e. Cardiio Rhythm iPhone AF-detection system or AliveCor single-lead ECG device) 2 to 18 months after procedure with or without antiarrhythmic medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean blood pressure as measured by 24-hour ambulatory blood pressure monitoring.</measure>
    <time_frame>18 months</time_frame>
    <description>The mean blood pressure as measured by 24-hour ambulatory blood pressure before and after ablation up to 36 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of peri-procedural complications.</measure>
    <time_frame>18 months</time_frame>
    <description>Incidence of peri-procedural complications, including stroke, PV stenosis, cardiac perforation, phrenic nerve palsy, esophageal injury and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure duration</measure>
    <time_frame>duing procedure</time_frame>
    <description>Procedure duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluoroscopy time during procedure</measure>
    <time_frame>dueing procedure</time_frame>
    <description>Fluoroscopy time during procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of repeat procedures</measure>
    <time_frame>18 months</time_frame>
    <description>Number of repeat procedures</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Pulmonary vein isolation alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PVI by cryo-balloon ablation without linear ablation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Renal nerve denervation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PVI by cryo-balloon ablation without linear ablation plus bilateral RND using a multi-electrode renal denervation catheter.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Renal Nerve Denervation</intervention_name>
    <description>Bilateral renal denervation using a multi-polar radiofrequency ablation catheter (Symplicity™ Spyral Cather, Medtronic) in the right and left main, branch, and accessory renal arteries in vessels ranging in diameter between 3 and 8 mm.</description>
    <arm_group_label>Renal nerve denervation</arm_group_label>
    <other_name>Renal artery sympathetic nerve denervation</other_name>
    <other_name>RND</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pulmonary vein isolation</intervention_name>
    <description>PVI by cryo-balloon ablation without linear ablation</description>
    <arm_group_label>Pulmonary vein isolation alone</arm_group_label>
    <arm_group_label>Renal nerve denervation</arm_group_label>
    <other_name>PVI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients age is 18 years or greater;&#xD;
&#xD;
          2. Patients undergoing a first-time ablation procedure for AF;&#xD;
&#xD;
          3. Patients with persistent AF;&#xD;
&#xD;
          4. Persistent AF will be defined as a sustained episode lasting &gt; 7 days and less than 3&#xD;
             years.&#xD;
&#xD;
          5. Patients with symptomatic AF that is refractory to at least one antiarrhythmic&#xD;
             medication;&#xD;
&#xD;
          6. Symptomatic patients are those who have been aware of their AF at any time within the&#xD;
             last 5 years prior to enrollment. Symptoms may include, but are not restricted to,&#xD;
             palpitations, shortness of breath, chest pain, fatigue, left ventricular dysfunction,&#xD;
             or other symptoms, or any combination of the above.&#xD;
&#xD;
          7. At least one episode of persistent AF must have been documented by ECG, Holter, loop&#xD;
             recorder, telemetry, trans telephonic monitoring (TTM), or implantable device within&#xD;
             last 2 years of enrollment in this investigation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with paroxysmal AF;&#xD;
&#xD;
          2. Paroxysmal AF will be defined as a sustained episode lasting &lt; 7 days.&#xD;
&#xD;
          3. Patients with long-standing persistent AF;&#xD;
&#xD;
          4. Long-standing persistent AF will be defined as a sustained episode lasting more than 3&#xD;
             years;&#xD;
&#xD;
          5. Patients for whom cardioversion or sinus rhythm will never be attempted/pursued;&#xD;
&#xD;
          6. Patients with AF felt to be secondary to an obvious reversible cause;&#xD;
&#xD;
          7. Patients with contraindications to systemic anticoagulation with heparin or warfarin&#xD;
             or a direct thrombin inhibitor;&#xD;
&#xD;
          8. Patients with left atrial size ≥ 60 mm (2D echocardiography, parasternal long axis&#xD;
             view);&#xD;
&#xD;
          9. Patients with more than 50% renal artery stenosis identified by duplex ultrasound or&#xD;
             renal angiogram;&#xD;
&#xD;
         10. Patients in whom a renal stent has been in place for less than3 months;&#xD;
&#xD;
         11. Patients with prior renal artery stent placement, the artery segment beyond the stent&#xD;
             margins must be able to accommodate treatments;&#xD;
&#xD;
         12. Patients with the treatment zone for denervation in the renal artery have areas of&#xD;
             atheroma, severe fibromuscular dysplasia, calcification, and aneurysm that cannot be&#xD;
             avoided;&#xD;
&#xD;
         13. Patients with renal dysfunction as demonstrated by an estimated glomerular filtration&#xD;
             rate less than 45 mL/min per 1.73 m2 are excluded from both studies;&#xD;
&#xD;
         14. Pregnant women;&#xD;
&#xD;
         15. Participation in another interventional study;&#xD;
&#xD;
         16. Patient with contraindication to left ventricle catheterization by a retrograde aortic&#xD;
             approach (eg mechanical aortic valve, severe aortic stenosis and aortic dissection).&#xD;
&#xD;
         17. Patient with systolic blood pressure &lt;100mmHg.&#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>Bryan Ping Yen YAN</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>October 18, 2021</last_update_submitted>
  <last_update_submitted_qc>October 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Professor Bryan Ping Yen YAN</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Ablation</keyword>
  <keyword>Renal Denervation</keyword>
  <keyword>Cryoballoon</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</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/NCT03246568
org study id: CUHK-CARD-2017-RND
nct id: NCT03246568
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Atrial fibrillation (AF) is the most common arrhythmia and it is associated with significant
      morbidity and mortality. Electrical isolation of the pulmonary vein (PVI) by radiofrequency
      energy or cryoablation has been shown to be an effective treatment of AF by reducing
      morbidity, improving quality of life and functional capacity.

      Renal artery sympathetic denervation (RND) by catheter ablation has been shown in a
      preliminary study to improve outcome of PVI in patients with paroxysmal and/or persistent AF
      with concomitant refractory or moderate hypertension. In patients with renal impairment, RND
      also conferred benefit in reducing AF recurrence after PVI. The initial indication for
      catheter-based RND is for blood pressure control in patients with resistant hypertension.
      However, a recent study failed to show significant difference in blood pressure reduction by
      RND. Therefore, the effect of RND on AF suppression may be independent of blood pressure
      control. Possible mechanisms of RND on AF may include risk factors modification and
      anti-arrhythmic effect.
This prospective randomized study aimed to evaluate the effect of RDN added to PVI for
      persistent AF. Study will be performed in accordance with Declaration of Helsinki.

      Study Hypothesis: Catheter based RDN can prevent recurrence of AF in patient with persistent
      AF undergoing PVI by mechanism not related to hypertension control.

      Primary outcome measure: Freedom from documented AF episodes post PVI as defined by longer
      than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure
      with or without antiarrhythmic medication.

      Sample Size:

      This is an exploratory study, the sample size calculation will not be applied and arbitrary
      assign 20 subjects to each arm will be adopted.

      Randomization Arms:

      Patients are randomized in 1:1 fraction to one of the following arms:

        1. PVI by cryo-balloon ablation without linear ablation;

        2. PVI by cryo-balloon ablation without linear ablation plus bilateral RND using a
           multi-electrode renal denervation catheter.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Research on the Basis of Earlier Theory Renal artery sympathetic denervation (RND) by catheter ablation has been shown in a preliminary study to improve outcome of electrical isolation of the pulmonary vein (PVI) in patients with paroxysmal and/or persistent AF with concomitant refractory hypertension and the same group later showed renal sympathetic denervation improved outcome of PVI in the cohort of paroxysmal and/or persistent AF patients with moderate hypertension. In patients with renal impairment, RND also conferred benefit in reducing AF recurrence after PVI.The initial indication for catheter-based RND is for blood pressure control in patients with resistant hypertension. Early data from clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension.
primary purpose: Treatment
masking: None (Open Label)
measure: Freedom from documented AF episodes post PVI by implantable loop recorder by implantable loop recorder.
time frame: 2 to 18 months after procedure
description: Freedom from documented AF episodes post PVI as defined by longer than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.
measure: Freedom from documented atrial arrhythmia episodes post PVI by implantable loop recorder.
time frame: 2 to 18 months after procedure
description: Freedom from documented atrial arrhythmia episodes post PVI as defined by longer than 30 seconds of atrial arrhythmia recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.
measure: Freedom from symptomatic AF episodes post PVI by implantable loop recorder.
time frame: 2 to 18 months after procedure
description: Freedom from symptomatic AF episodes post PVI as defined by longer than 30 seconds of AF recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.
measure: Freedom from symptomatic atrial arrhythmia episodes post PVI by implantable loop recorder.
time frame: 2 to 18 months after procedure
description: Freedom from symptomatic atrial arrhythmia episodes post PVI as defined by longer than 30 seconds of atrial arrhythmia recorded by implantable loop recorder 2 to 18 months after procedure with or without antiarrhythmic medication.
measure: Freedom from documented AF episodes post PVI by hand-held smartphone device.
time frame: 2 to 18 months after procedure
description: Freedom from documented AF episodes post PVI as defined by 30 seconds of AF recorded by hand-held smartphone device (i.e. Cardiio Rhythm iPhone AF-detection system or AliveCor single-lead ECG device) 2 to 18 months after procedure with or without antiarrhythmic medication.
measure: The mean blood pressure as measured by 24-hour ambulatory blood pressure monitoring.
time frame: 18 months
description: The mean blood pressure as measured by 24-hour ambulatory blood pressure before and after ablation up to 36 months.
measure: Incidence of peri-procedural complications.
time frame: 18 months
description: Incidence of peri-procedural complications, including stroke, PV stenosis, cardiac perforation, phrenic nerve palsy, esophageal injury and death.
measure: Procedure duration
time frame: duing procedure
description: Procedure duration
measure: Fluoroscopy time during procedure
time frame: dueing procedure
description: Fluoroscopy time during procedure
measure: Number of repeat procedures
time frame: 18 months
description: Number of repeat procedures
arm group label: Pulmonary vein isolation alone
arm group type: Active Comparator
description: PVI by cryo-balloon ablation without linear ablation
arm group label: Renal nerve denervation
arm group type: Experimental
description: PVI by cryo-balloon ablation without linear ablation plus bilateral RND using a multi-electrode renal denervation catheter.
intervention type: Procedure
intervention name: Renal Nerve Denervation
description: Bilateral renal denervation using a multi-polar radiofrequency ablation catheter (Symplicity™ Spyral Cather, Medtronic) in the right and left main, branch, and accessory renal arteries in vessels ranging in diameter between 3 and 8 mm.
arm group label: Renal nerve denervation
other name: Renal artery sympathetic nerve denervation
other name: RND
intervention type: Procedure
intervention name: Pulmonary vein isolation
description: PVI by cryo-balloon ablation without linear ablation
arm group label: Pulmonary vein isolation alone
arm group label: Renal nerve denervation
other name: PVI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bryan Ping Yen YAN
role: Principal Investigator
affiliation: Chinese University of Hong Kong
facility: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Professor Bryan Ping Yen YAN
investigator title: Associate Professor
mesh term: Atrial Fibrillation
sharing ipd: No