<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/NCT01713270</url>
  </required_header>
  <id_info>
    <org_study_id>2012-SR-080</org_study_id>
    <nct_id>NCT01713270</nct_id>
  </id_info>
  <brief_title>Renal Sympathetic Denervation in Patients With Drug-resistant Hypertension and Symptomatic Atrial Fibrillation</brief_title>
  <acronym>RSDforAF</acronym>
  <official_title>Safety and Effectiveness Study of Percutaneous Catheter-based Renal Sympathetic Denervation in Patients With Drug-resistant Hypertension and Symptomatic Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital with Nanjing Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To study whether renal sympathetic denervation(RSD) is safe and effective in patients with&#xD;
      drug-resistant hypertension and symptomatic atrial fibrillation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atrial fibrillation(AF) is the most common arrhythmia, and its frequency increases with age.&#xD;
      Hemodynamic impairment and thromboembolic events related to AF result in significant&#xD;
      morbidity, mortality, and cost. Management of patients with AF involves 3&#xD;
      objectives-correction of the rhythm disturbance, rate control, and prevention of&#xD;
      thromboembolism. Regardless of whether the rate-control or rhythm-control strategy is&#xD;
      pursued, attention must also be directed to antithrombotic therapy for prevention of&#xD;
      thromboembolism. Pharmacological cardioversion approaches appear simple but are less&#xD;
      efficacious. The major risk is related to poor tolerance of side effects，drug-associated&#xD;
      toxicity，and proarrhythmic potentia1 of antiarrhythmic drugs. Radiofrequency catheter&#xD;
      ablation of AF has developed rapidly in recent years, but the number of AF recurrences during&#xD;
      the long-term follow-up was significant. In addition, the complications associated with AF&#xD;
      ablation procedures likely to result in prolonged hospitalization, long-term disability or&#xD;
      death. Hypertension is the most important risk factor for AF , Hypertension is associated&#xD;
      with left ventricular hypertrophy, impaired ventricular filling, left atrial enlargement, and&#xD;
      slowing of atrial conduction velocity. These changes in cardiac structure and physiology&#xD;
      favor the development and maintenance of AF, and they increase the risk of thromboembolic&#xD;
      complications. In patients with AF, aggressive treatment of hypertension may reverse the&#xD;
      structural changes in the heart, reduce thromboembolic complications, and retard or prevent&#xD;
      the occurrence of AF. Recently, many clinical researches have verified that Catheter-based&#xD;
      renal sympathetic denervation can safely be used to substantially reduce blood pressure,&#xD;
      reduce left ventricular hypertrophy, improve glucose tolerance and sleep apnea severity.&#xD;
      Simultaneously, a marked reduction in muscle and whole-body sympathetic-nerve activity(MSNA)&#xD;
      is apparent, with a decrease in renal and whole-body norepinephrine spillover. Left ventricle&#xD;
      hypertrophy, left atrial enlargement, high norepinephrine level，glucose tolerance abnormity&#xD;
      and obstructive sleep apnea are all recognized as independent risk factors for the&#xD;
      development and recurrence of AF. So, we design this randomized parallel control multi center&#xD;
      clinical study to demonstrate whether renal sympathetic denervation is safe and effective in&#xD;
      patients with hypertension and symptomatic atrial fibrillation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">July 2015</completion_date>
  <primary_completion_date type="Anticipated">October 2014</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in atrial fibrillation burden</measure>
    <time_frame>from Baseline and 12 months</time_frame>
    <description>to demonstrate the effect of RSD on AF burden in patients with drug-resistant hypertension and symptomatic AF.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>rate controlling in persistent AF patients</measure>
    <time_frame>from baseline to 12 months</time_frame>
    <description>to demonstrate the effect of RSD on rate controlling in persistent AF patients from baseline to 12 months post-randomization,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>office systolic blood pressure</measure>
    <time_frame>from baseline to 12 months</time_frame>
    <description>the change in office systolic blood pressure from baseline to 12 months post-randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in cardiac structure and function,autonomic nerve function,fasting blood glucose, glycated hemoglobin, blood lipid, apnea-hypopnea index, pulse wave velocity and quality of life</measure>
    <time_frame>from baseline to 12 months</time_frame>
    <description>changes in cardiac structure and function by echocardiogram (include left ventricular ejection fraction, left ventricular end-diastolic diameter, interventricular septum, left atrium diameter), autonomic nerve function (heart rate variability by Holter), fasting blood glucose, glycated hemoglobin, blood lipid, apnea-hypopnea index, pulse wave velocity and quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Hypertension</condition>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>renal sympathetic denervation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Contrast renal angiography was performed to localize and assess the renal arteries. Once the anatomy was deemed acceptable, the internally irrigated radiofrequency ablation catheter was introduced into each renal artery. This was then maneuvered within the renal artery to allow energy delivery in a circumferential, longitudinally staggered manner to minimize the chance of renal artery stenosis. About four to eight ablations at 10 W for 60 seconds each were performed in both renal arteries. After renal sympathetic denervation, patients with persistent AF accepted direct-current cardioversion immediately.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>drug therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in the drug treatment group will be followed-up at 3, 6, 9 and 12 months after randomization. All the patients in this group will take their baseline antihypertensive medication at the original doses, without any changes except when medically required. Antiarrhythmic drugs treatment is consistent in both arms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>renal sympathetic denervation</intervention_name>
    <description>Contrast renal angiography was performed to localize and assess the renal arteries for accessibility and appropriateness for RSD. Once the anatomy was deemed acceptable, the internally irrigated radiofrequency ablation catheter(Celsius Thermocool, Biosense Webster, Diamond Bar, California) was introduced into each renal artery. then was maneuvered within the renal artery to allow energy delivery in a circumferential, longitudinally staggered manner to minimize the chance of renal artery stenosis. About four to eight ablations at 10 W for 1 minute each were performed in both renal arteries. During ablation, the catheter system monitored tip temperature and impedance, altering radiofrequency energy delivery in response to a predetermined algorithm.</description>
    <arm_group_label>renal sympathetic denervation</arm_group_label>
    <other_name>renal denervation</other_name>
    <other_name>renal ablation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>drug</intervention_name>
    <description>Angiotensin converting enzyme inhibitors, angiotensin receptor antagonist, calcium antagonists, diuretic, beta adrenoceptor blocking agents, propafenone, amiodarone</description>
    <arm_group_label>drug therapy</arm_group_label>
    <arm_group_label>renal sympathetic denervation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Direct-Current Cardioversion</intervention_name>
    <description>After renal sympathetic denervation, Persistent AF individual (except intracardiac thrombus) accept Direct-Current Cardioversion within one week. anticoagulation (INR 2.0 to 3.0) is recommended for at least 3 weeks prior to and 4 weeks after cardioversion.</description>
    <arm_group_label>renal sympathetic denervation</arm_group_label>
    <other_name>Cardioversion</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Individual is ≥18 and ≤75 years of age&#xD;
&#xD;
          2. More than half a year for definite primary hypertension&#xD;
&#xD;
          3. Individual has a systolic blood pressure ≥160 mmHg (≥150 mmHg for type 2 diabetics)&#xD;
             based on an average of three office blood pressure readings measured&#xD;
&#xD;
          4. Individual is adhering to a stable drug regimen, including three or more&#xD;
             antihypertensive medications of which one is a diuretic, for a minimum of 14 days&#xD;
             prior to enrollment&#xD;
&#xD;
          5. At least 30 seconds on a rhythm strip in an ECG record and at least 1 AF outbreak&#xD;
             which was recorded by EGG and Holter during the preceding 6 months&#xD;
&#xD;
          6. Paroxysmal and persistent AF individual&#xD;
&#xD;
          7. Agree to attend experimental clinic and sign written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Secondary and white-coat hypertension&#xD;
&#xD;
          2. Permanent AF individual&#xD;
&#xD;
          3. Thrombus in left atrial appendage found by transesophageal echocardiography&#xD;
&#xD;
          4. Individual with severely enlarged left atria ≥55 mm&#xD;
&#xD;
          5. Individual has experienced renal artery stenosis, or a history of prior renal artery&#xD;
             intervention including balloon angioplasty or stenting, or ineligible conditions seen&#xD;
             on renal artery computed tomography angiogram inspection such as double renal artery&#xD;
             on one side, renal artery length ≤2 cm, diameter ≤4 mm, and distortion at incept sect&#xD;
&#xD;
          6. Individual has experienced a definite acute coronary syndrome in the past 3 months, or&#xD;
             a cerebrovascular accident and alimentary canal bleeding within 3 months&#xD;
&#xD;
          7. Individual has experienced sick sinus syndrome&#xD;
&#xD;
          8. reversible causes of AF, including alcohol abuse, surgery, electrocution, myocadial&#xD;
             infarction, pericarditis, myocarditis, pulmonary embolism or other pulmonary diseases,&#xD;
             hyperthyroidism, and other metabolic disorders&#xD;
&#xD;
          9. structural heart diseases such as congenital, valvular heart diseases and kinds of&#xD;
             cardiomyopathy&#xD;
&#xD;
         10. Individual is pregnant or nursing&#xD;
&#xD;
         11. Mental disorders - individual cannot complete follow-up or one the researcher thinks&#xD;
             is unfit to be included in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qijun Shan, professor</last_name>
    <role>Study Chair</role>
    <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Qijun Shan, professor</last_name>
    <phone>0086 025 68136407</phone>
    <email>qjshan@njmu.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>First Affiliated Hospital of Nanjing Medical University</name>
      <address>
        <city>Nanjing,</city>
        <state>Jiangsu</state>
        <zip>210000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qijun Shan, professor</last_name>
      <phone>0086 025 68136407</phone>
      <email>qjshan@njmu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2013</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>July 4, 2013</last_update_submitted>
  <last_update_submitted_qc>July 4, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The First Affiliated Hospital with Nanjing Medical University</investigator_affiliation>
    <investigator_full_name>Qijun Shan</investigator_full_name>
    <investigator_title>Professor，Director, Cardiac Arrhythmia Group</investigator_title>
  </responsible_party>
  <keyword>Hypertension</keyword>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Arrhythmias, Cardiac</keyword>
  <keyword>Heart Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_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/NCT01713270
org study id: 2012-SR-080
nct id: NCT01713270
lead sponsor: 
has dmc: Yes
To study whether renal sympathetic denervation(RSD) is safe and effective in patients with
      drug-resistant hypertension and symptomatic atrial fibrillation.
Atrial fibrillation(AF) is the most common arrhythmia, and its frequency increases with age.
      Hemodynamic impairment and thromboembolic events related to AF result in significant
      morbidity, mortality, and cost. Management of patients with AF involves 3
      objectives-correction of the rhythm disturbance, rate control, and prevention of
      thromboembolism. Regardless of whether the rate-control or rhythm-control strategy is
      pursued, attention must also be directed to antithrombotic therapy for prevention of
      thromboembolism. Pharmacological cardioversion approaches appear simple but are less
      efficacious. The major risk is related to poor tolerance of side effects，drug-associated
      toxicity，and proarrhythmic potentia1 of antiarrhythmic drugs. Radiofrequency catheter
      ablation of AF has developed rapidly in recent years, but the number of AF recurrences during
      the long-term follow-up was significant. In addition, the complications associated with AF
      ablation procedures likely to result in prolonged hospitalization, long-term disability or
      death. Hypertension is the most important risk factor for AF , Hypertension is associated
      with left ventricular hypertrophy, impaired ventricular filling, left atrial enlargement, and
      slowing of atrial conduction velocity. These changes in cardiac structure and physiology
      favor the development and maintenance of AF, and they increase the risk of thromboembolic
      complications. In patients with AF, aggressive treatment of hypertension may reverse the
      structural changes in the heart, reduce thromboembolic complications, and retard or prevent
      the occurrence of AF. Recently, many clinical researches have verified that Catheter-based
      renal sympathetic denervation can safely be used to substantially reduce blood pressure,
      reduce left ventricular hypertrophy, improve glucose tolerance and sleep apnea severity.
      Simultaneously, a marked reduction in muscle and whole-body sympathetic-nerve activity(MSNA)
      is apparent, with a decrease in renal and whole-body norepinephrine spillover. Left ventricle
      hypertrophy, left atrial enlargement, high norepinephrine level，glucose tolerance abnormity
      and obstructive sleep apnea are all recognized as independent risk factors for the
      development and recurrence of AF. So, we design this randomized parallel control multi center
      clinical study to demonstrate whether renal sympathetic denervation is safe and effective in
      patients with hypertension and symptomatic atrial fibrillation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in atrial fibrillation burden
time frame: from Baseline and 12 months
description: to demonstrate the effect of RSD on AF burden in patients with drug-resistant hypertension and symptomatic AF.
measure: rate controlling in persistent AF patients
time frame: from baseline to 12 months
description: to demonstrate the effect of RSD on rate controlling in persistent AF patients from baseline to 12 months post-randomization,
measure: office systolic blood pressure
time frame: from baseline to 12 months
description: the change in office systolic blood pressure from baseline to 12 months post-randomization
measure: changes in cardiac structure and function,autonomic nerve function,fasting blood glucose, glycated hemoglobin, blood lipid, apnea-hypopnea index, pulse wave velocity and quality of life
time frame: from baseline to 12 months
description: changes in cardiac structure and function by echocardiogram (include left ventricular ejection fraction, left ventricular end-diastolic diameter, interventricular septum, left atrium diameter), autonomic nerve function (heart rate variability by Holter), fasting blood glucose, glycated hemoglobin, blood lipid, apnea-hypopnea index, pulse wave velocity and quality of life.
arm group label: renal sympathetic denervation
arm group type: Experimental
description: Contrast renal angiography was performed to localize and assess the renal arteries. Once the anatomy was deemed acceptable, the internally irrigated radiofrequency ablation catheter was introduced into each renal artery. This was then maneuvered within the renal artery to allow energy delivery in a circumferential, longitudinally staggered manner to minimize the chance of renal artery stenosis. About four to eight ablations at 10 W for 60 seconds each were performed in both renal arteries. After renal sympathetic denervation, patients with persistent AF accepted direct-current cardioversion immediately.
arm group label: drug therapy
arm group type: Active Comparator
description: Patients in the drug treatment group will be followed-up at 3, 6, 9 and 12 months after randomization. All the patients in this group will take their baseline antihypertensive medication at the original doses, without any changes except when medically required. Antiarrhythmic drugs treatment is consistent in both arms.
intervention type: Procedure
intervention name: renal sympathetic denervation
description: Contrast renal angiography was performed to localize and assess the renal arteries for accessibility and appropriateness for RSD. Once the anatomy was deemed acceptable, the internally irrigated radiofrequency ablation catheter(Celsius Thermocool, Biosense Webster, Diamond Bar, California) was introduced into each renal artery. then was maneuvered within the renal artery to allow energy delivery in a circumferential, longitudinally staggered manner to minimize the chance of renal artery stenosis. About four to eight ablations at 10 W for 1 minute each were performed in both renal arteries. During ablation, the catheter system monitored tip temperature and impedance, altering radiofrequency energy delivery in response to a predetermined algorithm.
arm group label: renal sympathetic denervation
other name: renal denervation
other name: renal ablation
intervention type: Drug
intervention name: drug
description: Angiotensin converting enzyme inhibitors, angiotensin receptor antagonist, calcium antagonists, diuretic, beta adrenoceptor blocking agents, propafenone, amiodarone
arm group label: drug therapy
arm group label: renal sympathetic denervation
intervention type: Procedure
intervention name: Direct-Current Cardioversion
description: After renal sympathetic denervation, Persistent AF individual (except intracardiac thrombus) accept Direct-Current Cardioversion within one week. anticoagulation (INR 2.0 to 3.0) is recommended for at least 3 weeks prior to and 4 weeks after cardioversion.
arm group label: renal sympathetic denervation
other name: Cardioversion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Qijun Shan, professor
role: Study Chair
affiliation: The First Affiliated Hospital with Nanjing Medical University
last name: Qijun Shan, professor
phone: 0086 025 68136407
email: qjshan@njmu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: The First Affiliated Hospital with Nanjing Medical University
investigator full name: Qijun Shan
investigator title: Professor，Director, Cardiac Arrhythmia Group
mesh term: Hypertension
mesh term: Atrial Fibrillation