<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/NCT01728493</url>
  </required_header>
  <id_info>
    <org_study_id>40133.091.12</org_study_id>
    <nct_id>NCT01728493</nct_id>
  </id_info>
  <brief_title>Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment</brief_title>
  <acronym>PAGODE</acronym>
  <official_title>Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It is caused&#xD;
      by autonomous secretion of aldosterone, encompassing a group of disorders which is for 99%&#xD;
      predominated by unilateral aldosterone-producing adenoma (APA) and bilateral adrenal&#xD;
      hyperplasia (BAH). Diagnosis of PA is relevant for two reasons:&#xD;
&#xD;
        1. independent of the level of blood pressure, hypertension due to autonomous aldosterone&#xD;
           secretion causes more cardiovascular damage than essential hypertension;&#xD;
&#xD;
        2. PA requires specific treatment: adrenalectomy in case of APA and mineralocorticoid&#xD;
           receptor antagonists (MRA) in case of BAH.&#xD;
&#xD;
      Although previously presumed a rare condition (prevalence &lt;1%), PA is now estimated to affect&#xD;
      6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the&#xD;
      amount of cardiovascular damage and the available specific treatment, the question is raised&#xD;
      whether screening of PA should be introduced in Dutch general practice. To answer this&#xD;
      important question, several issues with regard to PA need to be elucidated:&#xD;
&#xD;
        1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence&#xD;
           in the Dutch population is still unknown;&#xD;
&#xD;
        2. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of&#xD;
           hypertension (mean eight years), data on characteristics of early diagnosed PA are&#xD;
           lacking. Proof of early cardiovascular damage would strengthen the case of screening for&#xD;
           PA and needs to be studied;&#xD;
&#xD;
        3. Consequently, the diagnostic delay has lead to lack of data on optimal treatment in&#xD;
           early PA. In the current guideline (NHG-guideline 'Cardiovascular risk management') a&#xD;
           regimen of antihypertensive drugs is advised, and only if hypertension is refractory for&#xD;
           &gt;6 months patients are referred. It is unknown if hypertension is resistant to therapy&#xD;
           in the initial phase of PA. If not, this would also argue for early biochemical&#xD;
           screening for PA, because even if blood pressure is controlled, the detrimental effect&#xD;
           of aldosterone itself will go on unopposed. It is therefore required to study the&#xD;
           response to antihypertensive drugs (not MRA) in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It&#xD;
      is caused by autonomous secretion of aldosterone, encompassing a group of disorders which is&#xD;
      for more than 99% predominated by unilateral aldosterone-producing adenoma (APA) and&#xD;
      bilateral adrenal hyperplasia (BAH). Diagnosis of PA is relevant for two reasons: 1)&#xD;
      independent of the level of blood pressure, hypertension due to autonomous aldosterone&#xD;
      secretion causes more cardiovascular damage than essential hypertension; 2) PA requires&#xD;
      specific treatment: adrenalectomy in case of APA and mineralocorticoid receptor antagonists&#xD;
      (MRA) in case of BAH.&#xD;
&#xD;
      Although previously presumed a rare condition (prevalence &lt;1%), PA is now estimated to affect&#xD;
      6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the&#xD;
      amount of cardiovascular damage and the available specific treatment, the question has been&#xD;
      raised whether screening of PA should be introduced in Dutch general practice. To answer this&#xD;
      important question, several issues with regard to PA need to be elucidated:&#xD;
&#xD;
        1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence&#xD;
           in the Dutch population is still unknown;&#xD;
&#xD;
        2. Up to now, the laboratory test for screening for PA, the aldosterone/renin ratio (ARR),&#xD;
           is primarily used in secondary care. The relation between the ARR and outcomes in&#xD;
           primary care is unknown;&#xD;
&#xD;
        3. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of&#xD;
           hypertension (mean eight years), data on characteristics of early diagnosed PA are&#xD;
           lacking. Indications of early cardiovascular damage would strengthen the case of&#xD;
           screening for PA and needs to be studied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>PAGODE part 1: prevalence</measure>
    <time_frame>4 months</time_frame>
    <description>Prevalence of primary aldosteronism in newly diagnosed hypertensive patients in Dutch general practice.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PAGODE part 2: organ damage</measure>
    <time_frame>4 weeks</time_frame>
    <description>Difference in cardiorenovascular damage in patients with versus without primary aldosteronism, based on a composite of the following parameters:&#xD;
Left ventricular mass index in g/m2;&#xD;
Intima-media thickness of carotid artery in mm;&#xD;
Pulse wave velocity in m/s;&#xD;
Central aortic blood pressure in mmHg;&#xD;
Flow-mediated dilation in %;&#xD;
Albuminuria in mg albumin per mmol creatinin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PAGODE part 3: blood pressure regulation</measure>
    <time_frame>4 months</time_frame>
    <description>Difference in reduction of daytime systolic ambulatory blood pressure measurement (ABPM) in patients with normokalemic primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during conventional antihypertensive therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PAGODE part 2: organ damage</measure>
    <time_frame>4 weeks</time_frame>
    <description>To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:&#xD;
Serum potassium;&#xD;
Low density lipoprotein;&#xD;
Total cholesterol to high density lipoprotein ratio.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAGODE part 3: blood pressure regulation</measure>
    <time_frame>4 months</time_frame>
    <description>To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:&#xD;
Reduction of daytime systolic ABPM in patients with primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during spironolactone (or eplerenone);&#xD;
Serum potassium response using conventional antihypertensive medication;&#xD;
Adverse effects using conventional antihypertensive medication;&#xD;
Serum potassium response using spironolactone (or eplerenone);&#xD;
Adverse effects using spironolactone (or eplerenone).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PAGODE part 2: organ damage</measure>
    <time_frame>4 weeks</time_frame>
    <description>To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:&#xD;
Serum sodium;&#xD;
Serum glucose;&#xD;
Diastolic blood pressure.</description>
  </other_outcome>
  <other_outcome>
    <measure>PAGODE part 3: blood pressure regulation</measure>
    <time_frame>4 months</time_frame>
    <description>To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:&#xD;
Reduction in 24 hour ABPM using conventional antihypertensive medication;&#xD;
Reduction in 24 hour ABPM using mineralocorticoid receptor antagonists.</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">700</enrollment>
  <condition>Primary Aldosteronism</condition>
  <condition>Primary Hyperaldosteronism</condition>
  <arm_group>
    <arm_group_label>Part 1</arm_group_label>
    <description>- newly diagnosed hypertensive patients in general practice</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2:</arm_group_label>
    <description>newly diagnosed hypertensive patients with primary aldosteronism&#xD;
newly diagnosed hypertensive patients with essential hypertension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3:</arm_group_label>
    <description>newly diagnosed hypertensive patients with normokalemic primary aldosteronism&#xD;
newly diagnosed hypertensive patients with essential hypertension</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Newly diagnosed hypertensive patients in general practice (primary care).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Part 1:&#xD;
&#xD;
          1. Newly diagnosed hypertensive patients (according to the NHG-guideline 'Cardiovascular&#xD;
             risk management');&#xD;
&#xD;
          2. 18 years or older;&#xD;
&#xD;
          3. No use of antihypertensive medication.&#xD;
&#xD;
        Part 2:&#xD;
&#xD;
          1. Patients with increased aldosterone/renin ratio;&#xD;
&#xD;
          2. Positive sodium loading test;&#xD;
&#xD;
          3. Written informed consent.&#xD;
&#xD;
        Part 2 + 3:&#xD;
&#xD;
          1. Patients with normal aldosterone/renin ratio;&#xD;
&#xD;
          2. Normal ARR;&#xD;
&#xD;
          3. Written informed consent.&#xD;
&#xD;
        Part 3:&#xD;
&#xD;
          1. Patients with increased aldosterone/renin ratio;&#xD;
&#xD;
          2. Positive sodium loading test;&#xD;
&#xD;
          3. Normokalemic;&#xD;
&#xD;
          4. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of antihypertensive medication;&#xD;
&#xD;
          2. Heart failure class II, III or IV (according to the New York Heart Association);&#xD;
&#xD;
          3. Pregnancy or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Radboud university medical center</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6500 HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <last_update_submitted>April 5, 2016</last_update_submitted>
  <last_update_submitted_qc>April 5, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 6, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Radboud University Medical Center</investigator_affiliation>
    <investigator_full_name>JDeinum</investigator_full_name>
    <investigator_title>Dr J Deinum</investigator_title>
  </responsible_party>
  <keyword>Prevalence</keyword>
  <keyword>Primary aldosteronism</keyword>
  <keyword>Organ damage</keyword>
  <keyword>Mineralocorticoid receptor antagonists</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperaldosteronism</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/NCT01728493
org study id: 40133.091.12
nct id: NCT01728493
lead sponsor: 
has dmc: No
Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It is caused
      by autonomous secretion of aldosterone, encompassing a group of disorders which is for 99%
      predominated by unilateral aldosterone-producing adenoma (APA) and bilateral adrenal
      hyperplasia (BAH). Diagnosis of PA is relevant for two reasons:

        1. independent of the level of blood pressure, hypertension due to autonomous aldosterone
           secretion causes more cardiovascular damage than essential hypertension;

        2. PA requires specific treatment: adrenalectomy in case of APA and mineralocorticoid
           receptor antagonists (MRA) in case of BAH.

      Although previously presumed a rare condition (prevalence <1%), PA is now estimated to affect
      6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the
      amount of cardiovascular damage and the available specific treatment, the question is raised
      whether screening of PA should be introduced in Dutch general practice. To answer this
      important question, several issues with regard to PA need to be elucidated:

        1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence
           in the Dutch population is still unknown;

        2. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of
           hypertension (mean eight years), data on characteristics of early diagnosed PA are
           lacking. Proof of early cardiovascular damage would strengthen the case of screening for
           PA and needs to be studied;

        3. Consequently, the diagnostic delay has lead to lack of data on optimal treatment in
           early PA. In the current guideline (NHG-guideline 'Cardiovascular risk management') a
           regimen of antihypertensive drugs is advised, and only if hypertension is refractory for
           >6 months patients are referred. It is unknown if hypertension is resistant to therapy
           in the initial phase of PA. If not, this would also argue for early biochemical
           screening for PA, because even if blood pressure is controlled, the detrimental effect
           of aldosterone itself will go on unopposed. It is therefore required to study the
           response to antihypertensive drugs (not MRA) in these patients.
Rationale: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. It
      is caused by autonomous secretion of aldosterone, encompassing a group of disorders which is
      for more than 99% predominated by unilateral aldosterone-producing adenoma (APA) and
      bilateral adrenal hyperplasia (BAH). Diagnosis of PA is relevant for two reasons: 1)
      independent of the level of blood pressure, hypertension due to autonomous aldosterone
      secretion causes more cardiovascular damage than essential hypertension; 2) PA requires
      specific treatment: adrenalectomy in case of APA and mineralocorticoid receptor antagonists
      (MRA) in case of BAH.

      Although previously presumed a rare condition (prevalence <1%), PA is now estimated to affect
      6 to 20% of the hypertensive population. Given this high prevalence of PA, as well as the
      amount of cardiovascular damage and the available specific treatment, the question has been
      raised whether screening of PA should be introduced in Dutch general practice. To answer this
      important question, several issues with regard to PA need to be elucidated:

        1. International studies report a prevalence of PA in general practice of 6-13%. Prevalence
           in the Dutch population is still unknown;

        2. Up to now, the laboratory test for screening for PA, the aldosterone/renin ratio (ARR),
           is primarily used in secondary care. The relation between the ARR and outcomes in
           primary care is unknown;

        3. Because of underdiagnosis of PA and long delay in diagnosis of PA after recognition of
           hypertension (mean eight years), data on characteristics of early diagnosed PA are
           lacking. Indications of early cardiovascular damage would strengthen the case of
           screening for PA and needs to be studied.
observational model: Case-Control
time perspective: Prospective
measure: PAGODE part 1: prevalence
time frame: 4 months
description: Prevalence of primary aldosteronism in newly diagnosed hypertensive patients in Dutch general practice.
measure: PAGODE part 2: organ damage
time frame: 4 weeks
description: Difference in cardiorenovascular damage in patients with versus without primary aldosteronism, based on a composite of the following parameters:
Left ventricular mass index in g/m2;
Intima-media thickness of carotid artery in mm;
Pulse wave velocity in m/s;
Central aortic blood pressure in mmHg;
Flow-mediated dilation in %;
Albuminuria in mg albumin per mmol creatinin.
measure: PAGODE part 3: blood pressure regulation
time frame: 4 months
description: Difference in reduction of daytime systolic ambulatory blood pressure measurement (ABPM) in patients with normokalemic primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during conventional antihypertensive therapy.
measure: PAGODE part 2: organ damage
time frame: 4 weeks
description: To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:
Serum potassium;
Low density lipoprotein;
Total cholesterol to high density lipoprotein ratio.
measure: PAGODE part 3: blood pressure regulation
time frame: 4 months
description: To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:
Reduction of daytime systolic ABPM in patients with primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during spironolactone (or eplerenone);
Serum potassium response using conventional antihypertensive medication;
Adverse effects using conventional antihypertensive medication;
Serum potassium response using spironolactone (or eplerenone);
Adverse effects using spironolactone (or eplerenone).
measure: PAGODE part 2: organ damage
time frame: 4 weeks
description: To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:
Serum sodium;
Serum glucose;
Diastolic blood pressure.
measure: PAGODE part 3: blood pressure regulation
time frame: 4 months
description: To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:
Reduction in 24 hour ABPM using conventional antihypertensive medication;
Reduction in 24 hour ABPM using mineralocorticoid receptor antagonists.
arm group label: Part 1
description: - newly diagnosed hypertensive patients in general practice
arm group label: Part 2:
description: newly diagnosed hypertensive patients with primary aldosteronism
newly diagnosed hypertensive patients with essential hypertension
arm group label: Part 3:
description: newly diagnosed hypertensive patients with normokalemic primary aldosteronism
newly diagnosed hypertensive patients with essential hypertension
Blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Radboud University Medical Center
investigator full name: JDeinum
investigator title: Dr J Deinum
mesh term: Hyperaldosteronism