<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/NCT03282266</url>
  </required_header>
  <id_info>
    <org_study_id>NFH20170501</org_study_id>
    <nct_id>NCT03282266</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension</brief_title>
  <acronym>PADN-CFDA</acronym>
  <official_title>A Randomised, Single-blind, Sham Operation-controlled Study to Evaluate the Safety and Efficacy of the Pulmonary Artery Denervation for the Treatment of Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing First Hospital, Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pulnovo Medical (Wuxi) Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangdong Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tianjin Medical University General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Anzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenyang Northern Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Second Affiliated Hospital of Chongqing Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tongji Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nanjing First Hospital, Nanjing Medical University</source>
  <oversight_info>
    <has_dmc>Yes</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 objective of this randomized control trial is to gain clinical insight on the use of&#xD;
      pulmonary artery denervation (PADN) for the treatment of pulmonary arterial hypertension&#xD;
      (PAH). The primary objective is to assess effectiveness and safety of PADN for the treatment&#xD;
      of PAH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current study is designed as a multicenter, randomized and prospective study aiming to&#xD;
      compare the change in 6-minute walk distance (6MWD) of PADN on PAH patients. Based on the&#xD;
      previous studies, the 6MWD was 13±24 m after 6-month treatment using target drugs. And our&#xD;
      previous data showed that 6MWD at 6-month after PADN procedure was 65±85 m. As a result, a&#xD;
      total of 128 patients with Group I PAH are randomized at a ratio of 1:1 to either PADN&#xD;
      procedure plus phosphodiesterase-5 inhibitors (PDE5i) group (PADN group) or sham-PADN&#xD;
      procedure plus PDE5i group (Sham group) using a randomization schedule blocked by site. The&#xD;
      combination therapy of PDE5i with additional other PAH-specific target drugs is not&#xD;
      recommended for all patients and is left at physician's discretion in both groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 18, 2018</start_date>
  <completion_date type="Actual">December 22, 2021</completion_date>
  <primary_completion_date type="Actual">June 22, 2021</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 (Participant)</masking>
    <masking_description>sham operation</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in 6-Minute Walk Distance (6MWD) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Systolic Pulmonary Arterial Pressure (sPAP) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>sPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>mPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Cardiac Output (CO) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>CO is the volume of blood being pumped by the heart ventricle in the time interval of one minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pulmonary Vascular Resistance (PVR) at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Right Ventricle Functional at 6 Month</measure>
    <time_frame>Baseline, 6 Month</time_frame>
    <description>Right ventricle functional measures by echocardiography include right ventricle systolic and diastolic functional variables.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAH-related events</measure>
    <time_frame>6 Month</time_frame>
    <description>PAH-related events were defined as those caused by worsening of PAH, initiation of treatment with intravenous or subcutaneous prostanoids, lung transplantation, atrial septostomy, or all-cause mortality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">128</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>PADN + 5-phosphodiesterase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A total of 64 patients are assigned to PADN + 5-phosphodiesterase group after randomization schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham operation + 5-phosphodiesterase</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>A total of 64 patients are assigned to sham operation + 5-phosphodiesterase group after randomization schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>PADN</intervention_name>
    <description>PADN was performed at three sites at the conjunctional area between the distal main trunk and the ostial left branch. The following ablation parameters were programmed at each point: a temperature of 45 ℃-50 ℃, energy ≤15 W, and a time of 120 seconds. The procedure would cease for 10 seconds if the patient felt intolerable chest pain during the procedure. The EKG and pressure lines (including cardiac output) were monitored and continuously recorded throughout the procedure.</description>
    <arm_group_label>PADN + 5-phosphodiesterase</arm_group_label>
    <other_name>pulmonary artery denervation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham operation</intervention_name>
    <description>The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.</description>
    <arm_group_label>Sham operation + 5-phosphodiesterase</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Provision of informed consent prior to any study specific procedures; Men and women 18&#xD;
        years and older; Group I PAH, defined as a mPAP≥25mmHg, PCWP&lt;15mmHg and PVR[The PVR&#xD;
        =(mPAP-PCWP)/CO]&gt;3.0 Woods unit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General exclusion criteria:&#xD;
&#xD;
        Pregnancy and breast feeding mother; Estimated life expectancy &lt; 12 months; Scheduled major&#xD;
        surgery in the next 6 months; Inability to follow the protocol and comply with follow-up&#xD;
        requirements or any other reason that the investigator feels would place the patient at&#xD;
        increased risk; Previous enrolment in this study or treatment with an investigational drug&#xD;
        or device under another study protocol in the past 30 days.&#xD;
&#xD;
        Procedural exclusion criteria:&#xD;
&#xD;
        WHO group II, III, IV, V PH Severe Renal dysfunction (Ccr&lt;30 ml/min) Blood platelet&#xD;
        count&lt;100,000/L Expected life span&lt;6-month Systematical inflammation Malignant cancer(s)&#xD;
        Tricuspid valve stenosis, Supra-pulmonary valve stenosis Allergic to studied drugs or metal&#xD;
        materials.&#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>Shao-Liang Chen, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Nanjing First Hospital, Nanjing Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nanjing First Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, Stone GW. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol. 2013 Sep 17;62(12):1092-1100. doi: 10.1016/j.jacc.2013.05.075. Epub 2013 Jul 10.</citation>
    <PMID>23850902</PMID>
  </reference>
  <reference>
    <citation>Chen SL, Zhang H, Xie DJ, Zhang J, Zhou L, Rothman AM, Stone GW. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ Cardiovasc Interv. 2015 Nov;8(11):e002837. doi: 10.1161/CIRCINTERVENTIONS.115.002837.</citation>
    <PMID>26553699</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>March 26, 2022</last_update_submitted>
  <last_update_submitted_qc>March 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanjing First Hospital, Nanjing Medical University</investigator_affiliation>
    <investigator_full_name>HangZhang</investigator_full_name>
    <investigator_title>Vice Director of Cardiovascular Department</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</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/NCT03282266
org study id: NFH20170501
nct id: NCT03282266
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The objective of this randomized control trial is to gain clinical insight on the use of
      pulmonary artery denervation (PADN) for the treatment of pulmonary arterial hypertension
      (PAH). The primary objective is to assess effectiveness and safety of PADN for the treatment
      of PAH.
The current study is designed as a multicenter, randomized and prospective study aiming to
      compare the change in 6-minute walk distance (6MWD) of PADN on PAH patients. Based on the
      previous studies, the 6MWD was 13±24 m after 6-month treatment using target drugs. And our
      previous data showed that 6MWD at 6-month after PADN procedure was 65±85 m. As a result, a
      total of 128 patients with Group I PAH are randomized at a ratio of 1:1 to either PADN
      procedure plus phosphodiesterase-5 inhibitors (PDE5i) group (PADN group) or sham-PADN
      procedure plus PDE5i group (Sham group) using a randomization schedule blocked by site. The
      combination therapy of PDE5i with additional other PAH-specific target drugs is not
      recommended for all patients and is left at physician's discretion in both groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: sham operation
measure: Change From Baseline in 6-Minute Walk Distance (6MWD) at 6 Month
time frame: Baseline, 6 Month
description: 6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
measure: Change From Baseline in Systolic Pulmonary Arterial Pressure (sPAP) at 6 Month
time frame: Baseline, 6 Month
description: sPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
measure: Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at 6 Month
time frame: Baseline, 6 Month
description: mPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
measure: Change From Baseline in Cardiac Output (CO) at 6 Month
time frame: Baseline, 6 Month
description: CO is the volume of blood being pumped by the heart ventricle in the time interval of one minute.
measure: Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 6 Month
time frame: Baseline, 6 Month
description: PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 6 Month
time frame: Baseline, 6 Month
description: PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).
measure: Change From Baseline in Right Ventricle Functional at 6 Month
time frame: Baseline, 6 Month
description: Right ventricle functional measures by echocardiography include right ventricle systolic and diastolic functional variables.
measure: PAH-related events
time frame: 6 Month
description: PAH-related events were defined as those caused by worsening of PAH, initiation of treatment with intravenous or subcutaneous prostanoids, lung transplantation, atrial septostomy, or all-cause mortality.
arm group label: PADN + 5-phosphodiesterase
arm group type: Experimental
description: A total of 64 patients are assigned to PADN + 5-phosphodiesterase group after randomization schedule.
arm group label: Sham operation + 5-phosphodiesterase
arm group type: Sham Comparator
description: A total of 64 patients are assigned to sham operation + 5-phosphodiesterase group after randomization schedule.
intervention type: Procedure
intervention name: PADN
description: PADN was performed at three sites at the conjunctional area between the distal main trunk and the ostial left branch. The following ablation parameters were programmed at each point: a temperature of 45 ℃-50 ℃, energy ≤15 W, and a time of 120 seconds. The procedure would cease for 10 seconds if the patient felt intolerable chest pain during the procedure. The EKG and pressure lines (including cardiac output) were monitored and continuously recorded throughout the procedure.
arm group label: PADN + 5-phosphodiesterase
other name: pulmonary artery denervation
intervention type: Procedure
intervention name: Sham operation
description: The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.
arm group label: Sham operation + 5-phosphodiesterase
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shao-Liang Chen, MD, PhD
role: Study Chair
affiliation: Nanjing First Hospital, Nanjing Medical University
facility: 
country: China
citation: Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, Stone GW. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol. 2013 Sep 17;62(12):1092-1100. doi: 10.1016/j.jacc.2013.05.075. Epub 2013 Jul 10.
PMID: 23850902
citation: Chen SL, Zhang H, Xie DJ, Zhang J, Zhou L, Rothman AM, Stone GW. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ Cardiovasc Interv. 2015 Nov;8(11):e002837. doi: 10.1161/CIRCINTERVENTIONS.115.002837.
PMID: 26553699
responsible party type: Principal Investigator
investigator affiliation: Nanjing First Hospital, Nanjing Medical University
investigator full name: HangZhang
investigator title: Vice Director of Cardiovascular Department
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
sharing ipd: No