MRA and ARB Treatment in Screening of Primary Aldosteronism

NCT04185857 | Completed DMC

• 1 other identifier: EMIRA-64140
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Aldosteronism Due to Aldosterone Producing Adenoma

Keywords

renin; aldosterone; aldosterone to renin ratio

Outcome Measures

Primary Outcomes (1)

• Aldosterone to renin ratio (ARR)

  ARR measured as ng/mIU after treatment with canrenone, or olmesartan on top of canrenone

  one month

Secondary Outcomes (2)

• Serum potassium levels

  one month

• Blood pressure

  one month

Study Arms (1)

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; Drug: olmesartan 10-20 mg orally once a day

Interventions

canrenone 50-100 mg orally once a day DRUG

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.

Patients with primary aldosteronism (PA)

olmesartan 10-20 mg orally once a day DRUG

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.

Patients with primary aldosteronism (PA)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive PA patients subtyped with adrenal vein sampling (AVS) at the University of Padova, Italy

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Padova: lead

Study Sites (1)

Department of Medicine - DIMED, University of Padova, Italy

Padua, Italy

Location

Related Publications (5)

• Rossitto G, Cesari M, Ceolotto G, Maiolino G, Seccia TM, Rossi GP. Effects of mineralocorticoid and AT-1 receptor antagonism on the aldosterone-renin ratio (ARR) in primary aldosteronism patients (EMIRA Study): rationale and design. J Hum Hypertens. 2019 Feb;33(2):167-171. doi: 10.1038/s41371-018-0139-x. Epub 2018 Dec 5.

  PMID: 30518805 RESULT

• Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F; PAPY Study Investigators. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006 Dec 5;48(11):2293-300. doi: 10.1016/j.jacc.2006.07.059. Epub 2006 Nov 13.

  PMID: 17161262 RESULT

• Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, Papadopoulos N, Vogiatzis K, Zamboulis C. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet. 2008 Jun 7;371(9628):1921-6. doi: 10.1016/S0140-6736(08)60834-X.

  PMID: 18539224 RESULT

• Seccia TM, Caroccia B, Gomez-Sanchez EP, Gomez-Sanchez CE, Rossi GP. The Biology of Normal Zona Glomerulosa and Aldosterone-Producing Adenoma: Pathological Implications. Endocr Rev. 2018 Dec 1;39(6):1029-1056. doi: 10.1210/er.2018-00060.

  PMID: 30007283 RESULT

• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.

  PMID: 26934393 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Interventions

Canrenone; olmesartan

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Gian Paolo Rossi

  University of Padova

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 4, 2019
• Study Start: January 1, 2018
• Primary Completion: October 1, 2019
• Study Completion: October 25, 2019
• Last Updated: December 4, 2019

Record last verified: 2019-12

Locations

IT (1)