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MRA and ARB Treatment in Screening of Primary Aldosteronism (EMIRA)

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ClinicalTrials.gov Identifier: NCT04185857
Recruitment Status : Completed
First Posted : December 4, 2019
Last Update Posted : December 4, 2019
Sponsor:
Information provided by (Responsible Party):
Gian Paolo Rossi, MD, FAHA, FACC, University Hospital Padova

Brief Summary:
Current guidelines recommend withdrawal of treatments that affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). However, abandonment of mineralocorti-coid-receptor antagonist (MRA) and/or blockers of the renin-angiotensin system can deteriorate control of blood pressure (BP) and hypokalemia. Thus, in consecutive patients with an unambiguous diagnosis of PA in wash-out from confounding treatments and subtyped by AVS, the investigators have compared within-patient the plasma aldosterone and active renin concentration, and the ARR values, measured at baseline, and after a one-month treatment with MRA alone and combined with an AT-1 receptor blocker (ARB). Patients on a regular salt intake have been treated with canrenone (50-100 mg orally) for 1 month, after which olmesartan (10 or 20 mg orally) has been added for another month with up-titration of both treatments over the first 2 weeks to control BP and hypokalemia, however maintaining background therapy. The biochemical variables and the ARR have been assessed in an identical manner at baseline values and after each month of treatment. The investigators calculated that with a sample size of 40 patients the study will have a 95% power to show a clinically significant 20% change in the ARR at an 5% alfa-value using a two-sided paired t-test. Hence, this study will allow to determine if an MRA alone, or added to an ARB at doses that control BP and hypokalemia, affect or not the ARR, thus allow to establish if these agents can be administered or must be forbidden during the screening of PA.

Condition or disease Intervention/treatment
Primary Aldosteronism Due to Aldosterone Producing Adenoma Drug: canrenone 50-100 mg orally once a day Drug: olmesartan 10-20 mg orally once a day

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Study Type : Observational
Actual Enrollment : 50 participants
Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Effects of Mineralocorticoid and AT-1 Receptor Antagonism on the Aldosterone-Renin Ratio (ARR) In Primary Aldosteronism Patients (EMIRA Study): Rationale and Design
Actual Study Start Date : January 1, 2018
Actual Primary Completion Date : October 1, 2019
Actual Study Completion Date : October 25, 2019


Group/Cohort Intervention/treatment
Patients with primary aldosteronism (PA)

After two biochemical and clinical evaluations under baseline conditions PA patients will be treated with canrenone 50-100 mg orally once a day.

After one month of such therapy they will undergo the a clinical and biochemical evaluation (FW1). After, they will continue with a combination therapy with canrenone, plus olmesartan starting with 10 mg a day for oral administration, a dose that can be doubled, if necessary, to achieve normotension.

At the end of the second month of the double therapy, patients will undergo a biochemical re-evaluation at the Center of Hypertension (FW2).

Drug: canrenone 50-100 mg orally once a day
After two biochemical and clinical evaluations under baseline conditions and after pharmacological washout from diuretics, betablockers, ARBs or ACEI (about 4 weeks) and MRAs (abut 6 weeks), PA patients will be treated with canrenone 50-100 mg orally once a day. After 1 or 2 weeks the dose will be doubled if necessary to control BP and serum potassium.

Drug: olmesartan 10-20 mg orally once a day

After one month of treatment with canrenone the patients will undergo a clinical and biochemical evaluation (FW1) in a manner identical to the two basal evaluations. After, they will continue with a combination therapy with canrenone, at the dose reached, plus olmesartan starting with 10 mg a day for oral administration, a dose that could be doubled, if necessary, to achieve normotension.

At the end of the second month of the double therapy, patients will undergo a biochemical re-evaluation at the Center of Hypertension (FW2) with methods identical to those performed in the two baseline evaluations and after one month of canrenone.





Primary Outcome Measures :
  1. Aldosterone to renin ratio (ARR) [ Time Frame: one month ]
    ARR measured as ng/mIU after treatment with canrenone, or olmesartan on top of canrenone


Secondary Outcome Measures :
  1. Serum potassium levels [ Time Frame: one month ]
    Serum potassium measured as mmol/L after treatment with canrenone, or olmesartan on top of canrenone

  2. Blood pressure [ Time Frame: one month ]
    Blood pressure measured as mmol/L after treatment with canrenone, or olmesartan on top of canrenone


Biospecimen Retention:   Samples Without DNA
plasma


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive PA patients subtyped with adrenal vein sampling (AVS) at the University of Padova, Italy
Criteria

Inclusion Criteria:

  • age 18 - 75 years;
  • diagnosis of Aldosterone Producing Adenoma (APA);
  • written informed consent.

Exclusion Criteria:

  • refusal to participate to the study;
  • history of intolerance or allergy to canrenone or ARB.

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): NCT04185857


Locations
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Italy
Department of Medicine - DIMED, University of Padova, Italy
Padova, Italy
Sponsors and Collaborators
University Hospital Padova
Investigators
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Study Director: Gian Paolo Rossi University of Padova
Publications of Results:

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Responsible Party: Gian Paolo Rossi, MD, FAHA, FACC, Professor, University Hospital Padova
ClinicalTrials.gov Identifier: NCT04185857    
Other Study ID Numbers: EMIRA-64140
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: December 4, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Gian Paolo Rossi, MD, FAHA, FACC, University Hospital Padova:
renin
aldosterone
aldosterone to renin ratio
Additional relevant MeSH terms:
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Adenoma
Hyperaldosteronism
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Olmesartan
Canrenone
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents