<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/NCT04409431</url>
  </required_header>
  <id_info>
    <org_study_id>AAA-S</org_study_id>
    <nct_id>NCT04409431</nct_id>
  </id_info>
  <brief_title>Effects of Adrenal Artery Ablation and Spironolactone in Patients With Primary Aldosteronism</brief_title>
  <official_title>An Open-label, Cohort Study on Effects and Long-term Prognosis of Adrenal Artery Ablation and Spironolactone in Patients With Primary Aldosteronism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Third Military Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Third Military Medical University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary aldosteronism (PA) is one of the most common cause of endocrine and resistant&#xD;
      hypertension. Current studies have shown that the activation of the&#xD;
      renin-angiotensin-aldosterone system (RAAS) and the increased sympathetic nerve activity in&#xD;
      the central or local tissue are the key mechanisms of high blood pressure and its organ&#xD;
      damages.&#xD;
&#xD;
      Current guidelines suggest that surgery and aldosterone receptor inhibitors are the only&#xD;
      treatment for primary aldosteronism. However, only about 35% of aldosterone tumors and a&#xD;
      small number of unilateral adrenal hyperplasia can be treated surgically. More than 60% of&#xD;
      primary aldosteronism and bilateral adrenal hyperplasia need long-term oral aldosterone&#xD;
      receptor inhibitors. At present, spironolactone is the most commonly used aldosterone&#xD;
      receptor inhibitor. Long term use of spironolactone may cause hyperkalemia, hyperplasia of&#xD;
      male mammary gland, hairiness of female and other adverse reactions. Therefore, the&#xD;
      researchers suggest that partial removal of adrenals can reduce aldosterone level, lower&#xD;
      blood pressure and restore potassium metabolism balance.&#xD;
&#xD;
      In patients with primary hyperaldosteronism, the level of aldosterone increases, which can&#xD;
      cause vascular endothelial dysfunction, myocardial injury and ventricular fibrosis. The study&#xD;
      shows that long-term oral administration of spironolactone can reverse the above&#xD;
      cardiovascular damage and correct heart failure. Adrenal artery ablation can reduce&#xD;
      aldosterone level, but the long-term effect on cardiovascular system is unknown. In order to&#xD;
      confirm the effect of adrenal artery ablation on blood pressure and cardiovascular system,&#xD;
      the researchers conducted an open cohort study on patients with primary aldosteronism&#xD;
      (including aldosterone, idiopathic aldosteronism and adrenal hyperplasia). To observe the&#xD;
      effect of adrenal artery ablation and spironolactone on blood pressure, blood electrolyte,&#xD;
      metabolic index, cardiovascular events and cardiovascular death risk in patients with primary&#xD;
      aldosteronism, and to explore its efficacy and safety.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 1, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients in the Intervention group will be treated with endovascular chemical ablation of adrenal gland by endovascular injection of dehydrated alcohol. Patients in the Control group will be treated with spironolactone</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of office systolic and diastolic pressure compared with the baseline between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Change of office systolic and diastolic pressure compared with the baseline between the intervention and control group at the end of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of major adverse cardiac events (MACE)(%) between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Incidence of major adverse cardiac events (MACE)(%)（cardiac death, myocardial infarction and target vessel revascularisation） between two groups at the end of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of 24-h average systolic blood pressure between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Change of 24-h average systolic blood pressure between two groups at end of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of 24-h average diastolic blood pressure between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Change of 24-h average diastolic blood pressure between two groups at end of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups at end of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of carotid intima-media thickness assessed by carotid ultrasound between two groups</measure>
    <time_frame>3 years(End of Trial)</time_frame>
    <description>Change of carotid intima-media thickness assessed by carotid ultrasound between two groups at end of the study</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Primary Aldosteronism</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Adrenal Artery Ablation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the Intervention group will be treated with endovascular chemical ablation of adrenal gland by endovascular injection of dehydrated alcohol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Spironolactone</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in this group will be treated with aldosterone 20-80mg daily according to blood pressure</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endovascular chemical Ablation of Adrenal Gland</intervention_name>
    <description>Patients in this group will be treated with partial ablation of adrenal gland by endovascular injection of dehydrated alcohol</description>
    <arm_group_label>Adrenal Artery Ablation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary Aldosteronis diagnosed by increased Renin ratio (ARR) and serum aldosterone&#xD;
             levels ≥15 ng / dl, and confirmed by saline injection test or captopril inhibition&#xD;
             test.&#xD;
&#xD;
          -  Idiopathic aldosteronism, bilateral adrenal hyperplasia, and unilateral adrenal&#xD;
             hyperplasia with no superior secretion confirmed with adrenal CT and adrenal venous&#xD;
             blood (AVS).&#xD;
&#xD;
          -  The patients was diagnosed with aldosteronoma or unilateral adrenal hyperplasia but&#xD;
             refused to surgical excision.&#xD;
&#xD;
          -  Signed informed consent and agreed to participate in this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Aldosterone cancer.&#xD;
&#xD;
          -  Hyperkalemia.&#xD;
&#xD;
          -  Renal failure or the following history of nephropathy: serum creatinine 1.5 times&#xD;
             higher than the upper limit; dialysis history; or nephrotic syndrome.&#xD;
&#xD;
          -  Secondary hypertension except the primary aldosteronism.&#xD;
&#xD;
          -  Adrenergic insufficiency.&#xD;
&#xD;
          -  Heart failure with NYHA grade Ⅱ-Ⅳ grade or unstable angina, severe cardiovascular and&#xD;
             cerebrovascular stenosis, myocardial infarction, intracranial aneurysm, stroke and&#xD;
             other acute cardiovascular events.&#xD;
&#xD;
          -  Acute infections, tumors and severe arrhythmias, psychiatric disorders, drugs or&#xD;
             alcohol addicts.&#xD;
&#xD;
          -  Liver dysfunction or the following history of liver disease: AST or ALT 2 times higher&#xD;
             than the upper limit, liver cirrhosis, history of hepatic encephalopathy, esophageal&#xD;
             variceal history or portal shunt history.&#xD;
&#xD;
          -  Coagulation dysfunction.&#xD;
&#xD;
          -  Pregnant women or lactating women.&#xD;
&#xD;
          -  Participated in other clinical trials or admitted with other research drugs within 3&#xD;
             months prior to the trial.&#xD;
&#xD;
          -  Any surgical or medical condition which can significantly alter the absorption,&#xD;
             distribution, metabolism, or excretion of any study drug.&#xD;
&#xD;
          -  Allergy or any contraindications for the study drugs, contrast agents and alcohol.&#xD;
&#xD;
          -  Refused to sign informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhu ZM, MD</last_name>
    <role>Study Director</role>
    <affiliation>The third militery medical university</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Li Yingsha, MD</last_name>
    <phone>13594659454</phone>
    <phone_ext>68</phone_ext>
    <email>yslimiss@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhu ZM, MD</last_name>
    <phone>68767848</phone>
    <phone_ext>68-023</phone_ext>
    <email>zhuzm@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The third hospital affiliated to the Army Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Yingsha, MD</last_name>
      <phone>13594659454</phone>
      <phone_ext>68</phone_ext>
      <email>yslimiss@163.com</email>
    </contact>
    <investigator>
      <last_name>Zhu Zhiming, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>February 10, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>May 27, 2020</last_update_submitted>
  <last_update_submitted_qc>May 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Third Military Medical University</investigator_affiliation>
    <investigator_full_name>Zhiming Zhu</investigator_full_name>
    <investigator_title>Director of the department of Hypertension &amp; Endocrinology, Daping Hospital</investigator_title>
  </responsible_party>
  <keyword>Primary Aldosteronism</keyword>
  <keyword>Hypertension</keyword>
  <keyword>Adrenal Artery Ablation</keyword>
  <keyword>Spironolactone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Hyperaldosteronism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epinephrine</mesh_term>
    <mesh_term>Racepinephrine</mesh_term>
    <mesh_term>Epinephryl borate</mesh_term>
  </intervention_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/NCT04409431
org study id: AAA-S
nct id: NCT04409431
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Primary aldosteronism (PA) is one of the most common cause of endocrine and resistant
      hypertension. Current studies have shown that the activation of the
      renin-angiotensin-aldosterone system (RAAS) and the increased sympathetic nerve activity in
      the central or local tissue are the key mechanisms of high blood pressure and its organ
      damages.

      Current guidelines suggest that surgery and aldosterone receptor inhibitors are the only
      treatment for primary aldosteronism. However, only about 35% of aldosterone tumors and a
      small number of unilateral adrenal hyperplasia can be treated surgically. More than 60% of
      primary aldosteronism and bilateral adrenal hyperplasia need long-term oral aldosterone
      receptor inhibitors. At present, spironolactone is the most commonly used aldosterone
      receptor inhibitor. Long term use of spironolactone may cause hyperkalemia, hyperplasia of
      male mammary gland, hairiness of female and other adverse reactions. Therefore, the
      researchers suggest that partial removal of adrenals can reduce aldosterone level, lower
      blood pressure and restore potassium metabolism balance.

      In patients with primary hyperaldosteronism, the level of aldosterone increases, which can
      cause vascular endothelial dysfunction, myocardial injury and ventricular fibrosis. The study
      shows that long-term oral administration of spironolactone can reverse the above
      cardiovascular damage and correct heart failure. Adrenal artery ablation can reduce
      aldosterone level, but the long-term effect on cardiovascular system is unknown. In order to
      confirm the effect of adrenal artery ablation on blood pressure and cardiovascular system,
      the researchers conducted an open cohort study on patients with primary aldosteronism
      (including aldosterone, idiopathic aldosteronism and adrenal hyperplasia). To observe the
      effect of adrenal artery ablation and spironolactone on blood pressure, blood electrolyte,
      metabolic index, cardiovascular events and cardiovascular death risk in patients with primary
      aldosteronism, and to explore its efficacy and safety.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients in the Intervention group will be treated with endovascular chemical ablation of adrenal gland by endovascular injection of dehydrated alcohol. Patients in the Control group will be treated with spironolactone
primary purpose: Treatment
masking: None (Open Label)
measure: Change of office systolic and diastolic pressure compared with the baseline between two groups
time frame: 3 years(End of Trial)
description: Change of office systolic and diastolic pressure compared with the baseline between the intervention and control group at the end of the study
measure: Incidence of major adverse cardiac events (MACE)(%) between two groups
time frame: 3 years(End of Trial)
description: Incidence of major adverse cardiac events (MACE)(%)（cardiac death, myocardial infarction and target vessel revascularisation） between two groups at the end of the study
measure: Change of 24-h average systolic blood pressure between two groups
time frame: 3 years(End of Trial)
description: Change of 24-h average systolic blood pressure between two groups at end of the study
measure: Change of 24-h average diastolic blood pressure between two groups
time frame: 3 years(End of Trial)
description: Change of 24-h average diastolic blood pressure between two groups at end of the study
measure: Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups
time frame: 3 years(End of Trial)
description: Change of parameters assessed by echocardiography (IVSd、IVSs、LVPWd, LVPWs, LVEDD, LVEF, LVM) between two groups at end of the study
measure: Change of carotid intima-media thickness assessed by carotid ultrasound between two groups
time frame: 3 years(End of Trial)
description: Change of carotid intima-media thickness assessed by carotid ultrasound between two groups at end of the study
arm group label: Adrenal Artery Ablation
arm group type: Experimental
description: Patients in the Intervention group will be treated with endovascular chemical ablation of adrenal gland by endovascular injection of dehydrated alcohol.
arm group label: Spironolactone
arm group type: No Intervention
description: Patients in this group will be treated with aldosterone 20-80mg daily according to blood pressure
intervention type: Procedure
intervention name: Endovascular chemical Ablation of Adrenal Gland
description: Patients in this group will be treated with partial ablation of adrenal gland by endovascular injection of dehydrated alcohol
arm group label: Adrenal Artery Ablation
criteria: 
gender: All
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: No
last name: Zhu ZM, MD
role: Study Director
affiliation: The third militery medical university
last name: Li Yingsha, MD
phone: 13594659454
phone ext: 68
email: yslimiss@163.com
last name: Zhu ZM, MD
phone: 68767848
phone ext: 68-023
email: zhuzm@yahoo.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Third Military Medical University
investigator full name: Zhiming Zhu
investigator title: Director of the department of Hypertension & Endocrinology, Daping Hospital
mesh term: Hypertension
mesh term: Hyperaldosteronism
mesh term: Epinephrine
mesh term: Racepinephrine
mesh term: Epinephryl borate
sharing ipd: No