Clinical trial NCT00403910: Antiremodeling Effect Of Aldosterone Receptors Blockade With Canrenone In Mild Chronic Heart Failure. AREA IN-CHF Study
Official title: Phase 3 Study Of Antiremodeling Effect Of Aldosterone Receptors Blockade With Canrenone In Mild Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Lead sponsor: Heart Care Foundation
Sponsor class: OTHER
First posted: 2006-11-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: The protocol is sponsored by and independent organization and partially supported by Therabel

Eligibility criteria: 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

Primary outcomes:
measure: Changes in echocardiographic left ventricular diastolic volume
Secondary outcomes:
measure: Changes in left ventricular systolic volume
measure: Changes in ejection fraction
measure: Changes in NYHA class
measure: cardiac mortality
measure: hospitalization for cardiac causes
measure: combination of cardiac mortality hospitalizations for cardiac causes
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Presidio GM Lancisi
city: Avellino
country: Italy
facility: Az Ospedaliera Giuseppe Moscati
city: Aversa (CE)
country: Italy
facility: Presidio Ospedaliero Moscati
city: Barletta (BA)
country: Italy
facility: Ospedale Monsignor Angelo R di Miccoli
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Bologna
country: Italy
facility: Cardiologia Tiarini Corticella
city: Bolzano
country: Italy
facility: Ospedale Generale Provinciale
city: Cagliari
country: Italy
facility: Az Osp G Brotzu - S Michele
city: Caserta
country: Italy
facility: Az Ospedaliera S Anna e S Sebastiano
city: Cefalù (PA)
country: Italy
facility: Ospedale San Raffaele G Giglio
city: Empoli (FI)
country: Italy
facility: Ospedale Civile San Giuseppe
city: Feltre
country: Italy
facility: Ospedale Santa Maria del Prato
city: Francavilla Fontana (BR)
country: Italy
facility: Ospedale Civile Dario Camberlingo
city: Genova
country: Italy
facility: Az Osp-Univ San Martino
city: Ivrea
country: Italy
facility: Ospedale Civile
city: Milano
country: Italy
facility: Ospedale Fatebenefratelli
city: Modena
country: Italy
facility: Hepseria Hospital Modena SPA
city: Modena
country: Italy
facility: Ospedale Policlinico
city: Napoli
country: Italy
facility: Fondazione Evangelica Betania
city: Palermo
country: Italy
facility: Ospedale V Cervello
city: Passirana Rho (MI)
country: Italy
facility: Presidio Ospedaliero di Passirana
city: Pavia
country: Italy
facility: Ospedale Policlinico S Matteo IRCCS
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Pescia (PT)
country: Italy
facility: Ospedale della val di nievole
city: Pisa
country: Italy
facility: Azienda CREAS - IFC CNR San Cartaldo
city: Pontedera (PT)
country: Italy
facility: Ospedale Generale Provinciale Lotti
city: Ragusa (RG)
country: Italy
facility: Ospedale Civile
city: Rimini
country: Italy
facility: Ospedale Infermi
city: Roma
country: Italy
facility: Ospedale San Camillo
city: Roma
country: Italy
facility: Ospedale Sant'Andrea
city: Roma
country: Italy
facility: Ospedale Santo Spirito
city: Roma
country: Italy
facility: Policlinico Luigi di Liegro
city: Salerno
country: Italy
facility: Az Osp San Giovanni di Dio e Ruggi d'Aragona
city: San Bonifacio (VR)
country: Italy
facility: Ospedale G Fra Cristoforo
city: San Giovanni Rotondo (FG)
country: Italy
facility: Ospedale casa Sollievo della Sofferenza
city: Saronno
country: Italy
facility: Presidio Ospedaliero di Saronno
city: Sarzana (GE)
country: Italy
facility: Ospedale San Bartolomeo
city: Sassari
country: Italy
facility: Ospedale SS Annunziata
city: Sesto San Giovanni
country: Italy
facility: IRCCS Policlinico Multimedica
city: Telese Terme (BN)
country: Italy
facility: Fondazione S Maugeri Clinica del Lavoro
city: Tricase (LE)
country: Italy
facility: Ospedale Cardinale Panico
city: Trieste
country: Italy
facility: Az Osp-Univ Ospdali Riuniti
city: Vallo Della Lucania (SA)
country: Italy
facility: Ospedale San Luca
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Venezia
country: Italy
facility: Ospedali Civili Riuniti
Study officials:
affiliation: Ospedale San Giovanni di Roma
name: Alessandro Boccanelli, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.