Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment (PAGODE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01728493
Recruitment Status : Completed
First Posted : November 19, 2012
Last Update Posted : April 6, 2016
Sponsor:
Information provided by (Responsible Party):
JDeinum, Radboud University Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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.

Condition or disease
Primary Aldosteronism Primary Hyperaldosteronism

Detailed Description:

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.
Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Actual Enrollment : 700 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment
Study Start Date : September 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
Part 1
- newly diagnosed hypertensive patients in general practice
Part 2:
  • newly diagnosed hypertensive patients with primary aldosteronism
  • newly diagnosed hypertensive patients with essential hypertension
Part 3:
  • newly diagnosed hypertensive patients with normokalemic primary aldosteronism
  • newly diagnosed hypertensive patients with essential hypertension


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. PAGODE part 1: prevalence [ Time Frame: 4 months ]
    Prevalence of primary aldosteronism in newly diagnosed hypertensive patients in Dutch general practice.

  2. PAGODE part 2: organ damage [ Time Frame: 4 weeks ]

    Difference in cardiorenovascular damage in patients with versus without primary aldosteronism, based on a composite of the following parameters:

    1. Left ventricular mass index in g/m2;
    2. Intima-media thickness of carotid artery in mm;
    3. Pulse wave velocity in m/s;
    4. Central aortic blood pressure in mmHg;
    5. Flow-mediated dilation in %;
    6. Albuminuria in mg albumin per mmol creatinin.

  3. PAGODE part 3: blood pressure regulation [ Time Frame: 4 months ]
    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.


Secondary Outcome Measures :
  1. PAGODE part 2: organ damage [ Time Frame: 4 weeks ]

    To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

    1. Serum potassium;
    2. Low density lipoprotein;
    3. Total cholesterol to high density lipoprotein ratio.

  2. PAGODE part 3: blood pressure regulation [ Time Frame: 4 months ]

    To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

    1. Reduction of daytime systolic ABPM in patients with primary aldosteronism versus patients with essential hypertension in a standardized treatment regimen during spironolactone (or eplerenone);
    2. Serum potassium response using conventional antihypertensive medication;
    3. Adverse effects using conventional antihypertensive medication;
    4. Serum potassium response using spironolactone (or eplerenone);
    5. Adverse effects using spironolactone (or eplerenone).


Other Outcome Measures:
  1. PAGODE part 2: organ damage [ Time Frame: 4 weeks ]

    To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

    1. Serum sodium;
    2. Serum glucose;
    3. Diastolic blood pressure.

  2. PAGODE part 3: blood pressure regulation [ Time Frame: 4 months ]

    To observe differences between newly diagnosed hypertensive patients with versus without primary aldosteronism in:

    1. Reduction in 24 hour ABPM using conventional antihypertensive medication;
    2. Reduction in 24 hour ABPM using mineralocorticoid receptor antagonists.


Biospecimen Retention:   Samples With DNA
Blood

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Newly diagnosed hypertensive patients in general practice (primary care).
Criteria

Inclusion Criteria:

Part 1:

  1. Newly diagnosed hypertensive patients (according to the NHG-guideline 'Cardiovascular risk management');
  2. 18 years or older;
  3. No use of antihypertensive medication.

Part 2:

  1. Patients with increased aldosterone/renin ratio;
  2. Positive sodium loading test;
  3. Written informed consent.

Part 2 + 3:

  1. Patients with normal aldosterone/renin ratio;
  2. Normal ARR;
  3. Written informed consent.

Part 3:

  1. Patients with increased aldosterone/renin ratio;
  2. Positive sodium loading test;
  3. Normokalemic;
  4. Written informed consent.

Exclusion Criteria:

  1. Use of antihypertensive medication;
  2. Heart failure class II, III or IV (according to the New York Heart Association);
  3. Pregnancy or breastfeeding.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01728493


Locations
Layout table for location information
Netherlands
Radboud university medical center
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University Medical Center
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: JDeinum, Dr J Deinum, Radboud University Medical Center
ClinicalTrials.gov Identifier: NCT01728493    
Other Study ID Numbers: 40133.091.12
First Posted: November 19, 2012    Key Record Dates
Last Update Posted: April 6, 2016
Last Verified: April 2016
Keywords provided by JDeinum, Radboud University Medical Center:
Prevalence
Primary aldosteronism
Organ damage
Mineralocorticoid receptor antagonists
Additional relevant MeSH terms:
Layout table for MeSH terms
Hyperaldosteronism
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases