Antiremodeling Effect Of Aldosterone Receptors Blockade With Canrenone In Mild Chronic Heart Failure. AREA IN-CHF Study

Phase 3 Study Of Antiremodeling Effect Of Aldosterone Receptors Blockade With Canrenone In Mild Chronic Heart Failure

The RALES study has shown that spironolactone reduces the risk of morbidity and mortality both from progressive heart failure and sudden death, in patients with NYHA III or IV heart failure. This favourable effect was clearly independent from a diuretic effect. Antialdosterone drugs may be effective because they opposes the effects of aldosterone on sodium retention, loss of magnesium and potassium, sympathetic activation, baroreceptor function and vascular compliance. Antialdosterone treatment may also antagonize the effect of aldosterone in promoting cardiac fibrosis. In a RALES substudy baseline serum PIIINP, a marker of cardiac fibrosis synthesis showed an independent negative correlation with survival and CHF hospitalizations in the placebo group. Therefore it seems interesting to evaluate the effect of an Aldosterone receptor blocker on progression of left ventricular dysfunction in patients with mild heart failure assuming standard therapy.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Canrenone

Detailed Description

The protocol is sponsored by and independent organization and partially supported by Therabel

• Study Type: Interventional
• Enrollment: 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • Presidio GM Lancisi
  • Avellino, Italy
    • Az Ospedaliera Giuseppe Moscati
  • Aversa (CE), Italy
    • Presidio Ospedaliero Moscati
  • Barletta (BA), Italy
    • Ospedale Monsignor Angelo R di Miccoli
  • Bergamo, Italy
    • Ospedali Riuniti
  • Bologna, Italy
    • Cardiologia Tiarini Corticella
  • Bolzano, Italy
    • Ospedale Generale provinciale
  • Cagliari, Italy
    • Az Osp G Brotzu - S Michele
  • Caserta, Italy
    • Az Ospedaliera S Anna e S Sebastiano
  • Cefalù (PA), Italy
    • Ospedale San Raffaele G Giglio
  • Empoli (FI), Italy
    • Ospedale Civile San Giuseppe
  • Feltre, Italy
    • Ospedale Santa Maria del Prato
  • Francavilla Fontana (BR), Italy
    • Ospedale Civile Dario Camberlingo
  • Genova, Italy
    • Az Osp-Univ San Martino
  • Ivrea, Italy
    • Ospedale Civile
  • Milano, Italy
    • Ospedale Fatebenefratelli
  • Modena, Italy
    • Hepseria Hospital Modena SPA
  • Modena, Italy
    • Ospedale policlinico
  • Napoli, Italy
    • Fondazione Evangelica Betania
  • Palermo, Italy
    • Ospedale V Cervello
  • Passirana Rho (MI), Italy
    • Presidio Ospedaliero di Passirana
  • Pavia, Italy
    • Ospedale Policlinico S Matteo IRCCS
  • Perugia, Italy
    • Azienda Ospedaliera di Perugia
  • Pescia (PT), Italy
    • ospedale della Val di Nievole
  • Pisa, Italy
    • Azienda CREAS - IFC CNR San Cartaldo
  • Pontedera (PT), Italy
    • Ospedale Generale Provinciale Lotti
  • Ragusa (RG), Italy
    • Ospedale Civile
  • Rimini, Italy
    • Ospedale Infermi
  • Roma, Italy
    • Ospedale Sant'Andrea
  • Roma, Italy
    • Ospedale San Camillo
  • Roma, Italy
    • Ospedale Santo Spirito
  • Roma, Italy
    • Policlinico Luigi di Liegro
  • Salerno, Italy
    • Az Osp San Giovanni di Dio e Ruggi d'Aragona
  • San Bonifacio (VR), Italy
    • Ospedale G Fra Cristoforo
  • San Giovanni Rotondo (FG), Italy
    • Ospedale Casa Sollievo della Sofferenza
  • Saronno, Italy
    • Presidio Ospedaliero di Saronno
  • Sarzana (GE), Italy
    • Ospedale San Bartolomeo
  • Sassari, Italy
    • Ospedale SS Annunziata
  • Sesto San Giovanni, Italy
    • IRCCS Policlinico Multimedica
  • Telese Terme (BN), Italy
    • Fondazione S Maugeri Clinica del Lavoro
  • Tricase (LE), Italy
    • Ospedale Cardinale Panico
  • Trieste, Italy
    • Az Osp-Univ Ospdali Riuniti
  • Vallo Della Lucania (SA), Italy
    • Ospedale San Luca
  • Varese, Italy
    • Ospedale di Circolo e Fondazione Macchi
  • Venezia, Italy
    • Ospedali Civili Riuniti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Established diagnosis of congestive heart failure in NYHA class II
• Left ventricular ejection fraction <= 45% measured within 6 months from enrolment
• Stable standard heart failure therapy (if patients are on beta blocker drugs, treatment must have been started at least three months before enrolment)
• Informed consent (obtained prior of any study procedures)

Exclusion Criteria:

• Age <18 and >80
• Serum creatinine level > 2.5 mg per deciliter
• Serum potassium level > 5.0 mmol per liter
• Valvular heart disease amenable to surgical treatment
• Congenital heart disease
• Unstable angina and/or acute myocardial infarction and/or coronary revascularization procedure within three months before enrolment
• Intravenous therapy with inotropic drugs within three months before enrolment
• History of resuscitated ventricular fibrillation or tachycardia, unless these occurred within 24 hours of an acute myocardial infarction or the subject has an implanted an automatic cardioverter defibrillator
• Chronic active hepatitis or cirrhosis
• Malignant neoplasm or any life threatening non cardiac disease
• History of hypersensitivity to study drug
• Pregnancy or lactating or childbearing age women who are not protected by an accepted method of contraception
• History of drug or alcohol abuse
• Legal incapacity and/or other circumstances rending the patient unable to understand the nature, scope and possible consequences of the study.
• Evidence of uncooperative attitude
• Any condition other than heart failure that does not permit an optimal participation to the trial
• Participation to other RCTs during the last 3 months
• Treatment with: Lithium salts, Potassium sparing diuretics, oral positive inotropic drugs or any investigational drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Changes in echocardiographic left ventricular diastolic volume

Secondary Outcome Measures

Outcome Measure
Changes in left ventricular systolic volume
Changes in ejection fraction
Changes in NYHA class
cardiac mortality
hospitalization for cardiac causes
combination of cardiac mortality hospitalizations for cardiac causes

Collaborators and Investigators

• Sponsor: Heart Care Foundation
• Investigators: Study Chair: Alessandro Boccanelli, MD, Ospedale San Giovanni di Roma

Publications and helpful links

General Publications

• Cacciatore G, Boccanelli A, Mureddu GF, Maggioni AP, Latini R, Masson S, de Simone G; Investigatori dell' Area In-CHF. [The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design]. Ital Heart J. 2005 May;6 Suppl 1:66S-74S. Italian.
• de Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, Masson S, Vanasia M, Maggioni AP, Boccanelli A; AREA-in-CHF Investigators. Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study. Nutr Metab Cardiovasc Dis. 2011 Oct;21(10):783-91. doi: 10.1016/j.numecd.2010.02.012. Epub 2010 Jun 17.
• Clemenza F, Masson S, Conaldi PG, Di Carlo D, Boccanelli A, Mureddu GF, Gonzini L, Lucci D, Maggioni AP, Di Lenarda A, Nicolis EB, Vanasia M, Latini R; AREA IN-CHF Investigators. Galectin-3 and the Mineralocorticoid Receptor Antagonist Canrenone in Mild Heart Failure. Circ J. 2017 Sep 25;81(10):1543-1546. doi: 10.1253/circj.CJ-17-0656. Epub 2017 Aug 31.
• Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Di Lenarda A, Gavazzi A, Porcu M, Latini R, Lucci D, Maggioni AP, Masson S, Vanasia M, de Simone G; AREA IN-CHF Investigators. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail. 2009 Jan;11(1):68-76. doi: 10.1093/eurjhf/hfn015.
• Boccanelli A, Cacciatore G, Mureddu GF, de Simone G, Clemenza F, De Maria R, Di Lenarda A, Gavazzi A, Latini R, Masson S, Porcu M, Vanasia M, Gonzini L, Maggioni AP. Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure). J Cardiovasc Med (Hagerstown). 2007 Sep;8(9):683-91. doi: 10.2459/JCM.0b013e3281053a9a.

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Study Completion: July 1, 2006

Study Registration Dates

• First Submitted: November 24, 2006
• First Submitted That Met QC Criteria: November 24, 2006
• First Posted (ESTIMATE): November 27, 2006

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Canrenone
• Other Study ID Numbers: 17