Prevalence of Primary Aldosteronism in Hypertensive Patients Presenting With Atrial Flutter or Fibrillation (PAPPHY)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University Hospital Padova
Sponsor:
Information provided by (Responsible Party):
Gian Paolo Rossi, MD, FAHA, FACC, University Hospital Padova
ClinicalTrials.gov Identifier:
NCT01267747
First received: December 27, 2010
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

Primary objective of the PAPPHY Study is to establish the prevalence of primary aldosteronism (PA) in consecutive hypertensive patients hospitalized for lone (non valvular), paroxysmal, persistent or permanent atrial flutter or fibrillation (AFF).

Secondary objectives are to identify:

  1. the clinical, echocardiographic and biochemical predictors of AFF in the hypertensive patients with/without PA;
  2. if AFF, by increasing ANP and/o BNP thereby conceivably blunting aldosterone secretion, can lower the ARR and impede PA detection.
  3. the usefulness of the aldosterone-to-renin ratio (ARR) based on plasma renin activity (PRA) and the direct measurement of renin (DRA) for diagnosing PA in patients with AFF.
  4. the rate of recurrence or new onset AFF during follow-up in a cohort of hypertensive patients with/without PA as a function of specific treatment for the latter.

Design: cohort multicenter prospective study. Sample size: 1000 consecutive patients.

Procedure At baseline cardiac function, arterial stiffness, and plasma renin activity (PRA), direct renin assay (DRA), plasma aldosterone (PAC) will be measured. Pharmacologic or direct current cardioversion (DCC) will be performed if indicated according to 2010 ESC guidelines.

PRA and PAC will be measured again 2 weeks after cardioversion to answer secondary aim b.

If ARR is > 26 and PAC > 15 ng/dL, adrenal vein sampling (AVS) will be performed in patients willing to undergo adrenalectomy to identify a lateralized PAC excess.

Follow-up will be aimed at assessing damage organ, occurrence of cardiovascular events and recurrence of AFF in patients with or without PA.

Demonstration of a higher prevalence of PA in the patients with AFF as compared to the general population of the hypertensive subjects will provide evidence for 1) a role of aldosterone excess in causing AFF and cardiac electric remodeling; 2) the usefulness of case detection of PA in hypertensive patients with AFF; 3) the predictors of AFF; 4) the outcome of specific treatment for PA on risk of incident and recurrent AFF.


Condition
Atrial Fibrillation
Atrial Flutter
Aldosteronism

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Assessment of The Prevalence of Primary Aldosteronism in Hypertensive Patients Presenting With Atrial Flutter or Fibrillation

Resource links provided by NLM:


Further study details as provided by University Hospital Padova:

Primary Outcome Measures:
  • Prevalence of Primary Aldosteronism [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The prevalence of Primary Aldosteronism, as assessed as Aldosterone Renin Ratio > 26 ng/dL/ng/mL h) and PAC > 15 ng/dL, will be prospectively assessed in consecutive hypertensive patients hospitalized for lone (non valvular), paroxysmal, persistent or permanent AFF, at Internal Medicine, Cardiology and Endocrinology Units.


Secondary Outcome Measures:
  • Echocardiographic and biochemical variables predicting Primary Aldosteronism. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The clinical, echocardiographic and biochemical markers that can predict the risk for atrial fibrillation or flutter will be identified in the hypertensive patients with/without Primary Aldosteronism.

  • Aldosterone-to-renin ratio (ARR) based on plasma renin activity (PRA) and also on the direct measurement of active renin (DRA) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The diagnostic usefulness of the aldosterone-to-renin ratio (ARR) based on either plasma renin activity (PRA) or the direct measurement of active renin (DRA) will be prospectively determined for diagnosing primary aldosteronism in patients with atrial fibrillation or atrial flutter.

  • ARR for identification of PA as a function of the presence/absence of AFF [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The hypothesis being tested here is the following: AFF, by increasing ANP and/o BNP, could blunt aldosterone secretion. Hence the ARR could be lowered by the concurrence of AFF and this could impede the detection of PA in hypertensive patients.

  • Recurrence or new onset AFF in hypertensive patients with/without PA [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The rate of recurrence or new onset AFF during follow-up will be prospectively determined in a cohort of hypertensive patients with/without PA as a function of specific treatment for the latter.


Biospecimen Retention:   Samples With DNA

Venous blood will be withdrawn to measure

  • levels of ions (sodium, potassium, magnesium), creatinine, proBNP, and TSH in the serum, and
  • percent HbA1c levels, plasma aldosterone concentration (PAC), renin concentrations (DRA) and renin activity (PRA) in the plasma.

A venous blood specimen will be used to separate buffy coat for downstream identification of SNP associated with primary aldosteronism and development of atrial flutter or fibrillation.

Urine specimens will be collected to measure microalbuminuria.


Estimated Enrollment: 1000
Study Start Date: March 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Atrial fibrillation or flutter patients
Patients with atrial flutter or lone (non valvular), paroxysmal, persistent, or permanent atrial fibrillation consecutively admitted at Internal Medicine, Cardiology and Endocrinology Units.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Hypertensive patients presenting with atrial fibrillation or flutter AFF) at primary care European clinics (Internal Medicine, Cardiology, Endocrinology).

Criteria

Inclusion Criteria:

  • Unequivocal evidence (by ECG, Holter ECG or medical charts) of AFF (paroxysmal, persistent or permanent) in patients with blood pressure > 140/90 mmHg on at least 3 office measurements, or current use of anti-hypertensive drugs;
  • Written informed consent.

Exclusion Criteria:

  • Patient refusal to participate to the study;
  • Moderate-severe valvular or congenital or myocardial heart disease;
  • Current abnormal thyroid function;
  • Chronic renal failure (sCreatinine > 200 μM or eGFR < 40 ml/min, calculated with MDRD formula);
  • Hemochromatosis;
  • Alcohol abuse;
  • Acute coronary syndrome, or history of CABG, PTCA with/without stenting, acute myocardial infarction;
  • Hepatitis C virus and/or B and/or HIV infection;
  • Pheochromocytoma and other known secondary forms of arterial hypertension;
  • Hemodynamic instability precluding withdrawal of drugs (e.g. β-blockers, ARBs, ACE-I, diuretics), interfering with PRA (or DRA) and aldosterone measurements.

Patients with resistant hypertension in whom antihypertensive drug treatment withdrawal/modifications will be considered unsafe will be investigated on treatment and, if necessary, submitted to AVS to exclude a lateralized cause of aldosterone excess. They will be analyzed as a separate group.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01267747

Contacts
Contact: Gian Paolo Rossi, MD, FAHA 0039 049 8213 gianpaolo.rossi@unipd.it

Locations
Italy
Department of Medicine - DIMED, University of Padova, Italy Recruiting
Padova, Italy, 35128
Contact: Gian Paolo Rossi, MD, FAHA    0039 049 8217821    gianpaolo.rossi@unipd.it   
Sub-Investigator: Teresa M Seccia, MD, PhD         
Sub-Investigator: Valentina Gallina, MD         
Department of Medicine - DIMED, University of Padova, Italy Recruiting
Padova, Italy
Sub-Investigator: Please see the PAPY Study list of investigators Hypertension 2007; 50: 424         
Sponsors and Collaborators
University Hospital Padova
Investigators
Study Director: Gian Paolo Rossi, MD, FAHA Department of Medicine -DIMED, University Hospital of Padova, Italy
  More Information

Publications:

Responsible Party: Gian Paolo Rossi, MD, FAHA, FACC, MD, FAHA, FACC, University Hospital Padova
ClinicalTrials.gov Identifier: NCT01267747     History of Changes
Other Study ID Numbers: GPR-PAPPHY
Study First Received: December 27, 2010
Last Updated: March 26, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by University Hospital Padova:
Atrial fibrillation
Atrial Flutter
Primary Aldosteronism
Aldosterone Producing Adenoma

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Hyperaldosteronism
Adrenal Gland Diseases
Adrenocortical Hyperfunction
Arrhythmias, Cardiac
Cardiovascular Diseases
Endocrine System Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014