MedPath

GISSI-AF - Use of Valsartan an Angiotensin II AT1-Receptor Blocker in the Prevention of Atrial Fibrillation Recurrence

Phase 3
Completed
Conditions
Atrial Fibrillation
Interventions
Drug: Placebo
Registration Number
NCT00376272
Lead Sponsor
Gruppo di Ricerca GISSI
Brief Summary

Study purpose The purpose of the study is to show that the addition of valsartan on top of established therapies can reduce the recurrence of atrial fibrillation in patients with a history of recent atrial fibrillation associated with cardiovascular diseases/comorbidities.

Primary objective To demonstrate that, in patients with history of recent atrial fibrillation treated with the best recommended therapies, the addition of valsartan 320 mg is superior to placebo in reducing atrial fibrillation recurrence.

Study design The GISSI-AF is a prospective, multicenter, randomized, double blind, placebo controlled study. Patients with a history of atrial fibrillation will be centrally randomized in a 1:1 ratio to receive either valsartan or placebo.

GISSI-AF will be a pragmatic trial, with broad selection criteria to mimic real clinical practice as much as possible. Since no special examinations or procedures are required for the trial, the economic impact on the National Health Service will be minimized and use of resources likely to be optimized. The enrollment period will last 12 months. The patients will be followed up for 12 months from study entry

All prescribed treatments for AF or for the underlying cardiovascular diseases, including ACE-inhibitors, amiodarone and betablockers, will be allowed:

* patients should be on a stable treatment for at least one month

* the current guideline for hypertension treatment should be applied

* patients should not be started on ARBs during the study

Detailed Description

The protocol is sponsored by an independent organization and partially supported by Novartis

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1442
Inclusion Criteria
  1. Male or female patients >=40 years of age

  2. Sinus rhythm

  3. At least two ECG documented episodes of symptomatic AF in the previous 6 months or After a successful cardioversion for AF performed between 14 days and 48 hours before randomization

  4. At least one of the following underlying cardiovascular diseases/comorbidities:

    • heart failure/documented history of LV dysfunction (defined as an EF <40%)
    • history of hypertension >=6 months with/without LVH
    • Type II diabetes mellitus
    • documented history of stroke or peripheral vascular disease
    • documented history of coronary artery disease
    • lone atrial fibrillation with documented LA dilation (LA diameter >=45 mm for men and >=40 mm for women)
  5. Written informed consent to participate in the study prior to any study procedures

Exclusion Criteria
  1. Need for a continuous treatment with ARBs for any clinical reasons
  2. Contraindications or known hypersensitivity to ARBs
  3. Persistent standing systolic blood pressure < 110 mmHg
  4. Recent (<6 weeks) acute myocardial infarction or bypass surgery, or percutaneous coronary intervention
  5. Clinically significant valvular etiologies
  6. Thyroid dysfunction
  7. Indication for pacemaker or ICD implant or for an ablative treatment, recent (<6 months) PM or ICD implant, previous ablative treatment
  8. Planned cardiac surgery, expected to be performed within 3 months
  9. Serum creatinine level above 2.5 mg/dL
  10. Significant liver disease
  11. Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception
  12. Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol
  13. Presence of any non-cardiac disease (e.g. cancer) that is likely to significantly shorten life expectancy
  14. Treatment with any investigational agent within 1 month before randomization
  15. Currently decompensated heart failure

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1Valsartan-
2Placebo-
Primary Outcome Measures
NameTimeMethod
To demonstrate that, in patients with history of recent AF treated with the best recommended therapies, the addition of valsartan (titrated up to 320 mg daily) is superior to placebo in reducing over the whole follow-up:Time to first AF recurrence
First recurrence of AF,time to first AF recurrence
Rate of patients with more than one AF episode,end of follow-up
Secondary Outcome Measures
NameTimeMethod
Number of AF episodesend of fw-up
Number of hospitalizations for CV reasonsend of fw-up
Number of all-cause hospitalizationsend of fw-up
Incidence of thromboembolic eventsend of fw-up
Number of patients who die or with non-fatal thromboembolic eventsend of fw-up
Number of patients in sinus rhythm at the time of each study visitend of fw-up
Number of patients in sinus rhythm who did not have any prior AF recurrence during the studyend of fw-up
Duration and characteristics (ventricular rate) of the first recurrence of AF.end of fw-up

Trial Locations

Locations (107)

CTO

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Roma, RM, Italy

Ospedale Civile Saluzzo

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Saluzzo, CN, Italy

Ospedale Civile G. Mazzini

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Teramo, TE, Italy

Ospedale SS. Annunziata

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Taranto, TA, Italy

Casa di Cura Villa Verde

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Taranto, TA, Italy

Azienda USL 4 Terni

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Terni, TR, Italy

Ospedale San Giovanni

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Roma, RM, Italy

Ospedale Sant'Andrea

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Roma, RM, Italy

Ospedale di Cles

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Cles, TN, Italy

Ospedale Evangelico Valdese

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Torino, TO, Italy

Ospedale De Gironcoli

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Conegliano Veneto, TV, Italy

Azienda Servizi Sanitari N. 1 Triestina

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Trieste, TS, Italy

Ospedale Santa Maria dei Battuti

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Conegliano Veneto, TV, Italy

Policlinico Universitario Federico II

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Napoli, Italy

Ospedale Civile Pugliese

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Catanzaro, CZ, Italy

Ospedale Civile San Giovanni di Dio

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Crotone, KR, Italy

Policlinico Madonna della Consolazione

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Reggio Calabria, RC, Italy

Ospedali Riuniti Albano-Genzano

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Albano Laziale, RM, Italy

Presidio Ospedaliero

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Soriano Calabro, VV, Italy

Ospedale Civile

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Mirano, VE, Italy

Arcispedale Sant'Anna

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Ferrara, FE, Italy

Presidio Ospedaliero F. Ferrari

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Casarano, LE, Italy

Ospedale di Ialmicco - Palmanova - Udine

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Palmanova, UD, Italy

Ospedale S. Antonio

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San Daniele del Friuli, UD, Italy

Ospedale Civile Umberto I

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Mestre, VE, Italy

Azienda Ospedaliera Vincenzo Monaldi

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Napoli, Italy

Ospedale Santa Maria delle Grazie

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Pozzuoli, Italy

Ospedale Ave Gratia Plena

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San Felice a Cancello, CE, Italy

Ospedale Civile Ave Gratia Plena

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Piedimonte Matese, CE, Italy

Ospedale Santissima Annunziata

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Cosenza, CS, Italy

Ospedale San Francesco di Paola

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Paola, CS, Italy

Istituti Ospitalieri di Cremona

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Cremona, CR, Italy

Azienda Ospedaliera Mater Domini

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Località Germaneto - Catanzaro, CZ, Italy

Ospedale G. Basilotta

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Nicosia, EN, Italy

Ospedale Santa Maria Annunziata

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Bagno a Ripoli, FI, Italy

Ospedale San Carlo

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Genova-Voltri, GE, Italy

Ospedale Civile San Paolo

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Monfalcone, GO, Italy

Ospedale Civile Bassa Val di Cecina

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Cecina, LI, Italy

Ospedali Riuniti

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Livorno, LI, Italy

Ospedale del dono Svizzero

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Formia, LT, Italy

Istituto Clinico Humanitas

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Rozzano, MI, Italy

Ospedale Carlo Borella

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Giussano, MI, Italy

Ospedale San Raffaele

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Milano, MI, Italy

Nuovo Ospedale Civile di Sassuolo

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Sassuolo, MO, Italy

Ospedale Madonna delle Grazie

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Matera, MT, Italy

Multimedica SPA

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Sesto San Giovanni, MI, Italy

Ospedale Policlinico

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Modena, MO, Italy

Ospedale Buccheri La Ferla Fatebenefratelli

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Palermo, PA, Italy

A.R.N.A.S. Ospedale Civico e Benfratelli

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Palermo, PA, Italy

Ospedale V. Cervello

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Palermo, PA, Italy

Ospedale Civile San Massimo

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Penne, PE, Italy

Azienda Ospedaliera San Salvatore

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Pesaro, PU, Italy

Ospedale Generale Provinciale

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Este, PD, Italy

Ospedale Alta Valle del Tevere

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Città di Castello, PG, Italy

Presidio Ospedaliero Villa Sofia

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Palermo, PA, Italy

Nuovo Ospedale San Giovanni Battista

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Foligno, PG, Italy

Azienda Ospedaliera S. Maria degli Angeli

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Pordenone, PN, Italy

Ospedale Policlinico San Matteo IRCCS

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Pavia, PV, Italy

IRCCS - Fondazione Salvatore Maugeri

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Pavia, PV, Italy

Csa di Cura Villa Maria Cecilia

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Cotignola, RA, Italy

Ospedale Scillesi D'America

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Scilla, RC, Italy

Ospedale Civile G. Jazzolino

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Vibo Valentia, VV, Italy

Azienda Ospedaliera G. Brotzu - S. Michele

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Cagliari, CA, Italy

Ospedale Santa Barbara

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Rogliano, CS, Italy

Ospedale Civile Mellini

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Chiari, BS, Italy

Ospedali Riuniti di Bergamo

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Bergamo, BG, Italy

Casa di Cura Poliambulanza

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Brescia, BS, Italy

Ospedlae Generale Regionale

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Bolzano, BZ, Italy

Presidio Ospedaliero Mariano Santo

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Cosenza, CS, Italy

Nuovo Ospedale San Giovanni di Dio

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Firenze, FI, Italy

Ospedale San Bartolomeo

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Sarzana - Loc. Santa Caterina, SP, Italy

Azienda Ospedaliera - Univ. Ospedali Riuniti

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Trieste, TS, Italy

Ospedale di Bentivoglio

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Bentivoglio, BO, Italy

Ospedale Bellaria

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Bologna, BO, Italy

Azienda Ospedaliera Sant'Anna e San Sebastiano

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Caserta, CE, Italy

Azienda Ospedaliera Santa Croce e Carle

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Cuneo, CN, Italy

Ospedlae Maggiore

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Crema, CR, Italy

Ospedale Garibaldi - Nesima

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Catania, CT, Italy

Ospedale di Venere

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Bari - Carbonara, BA, Italy

Presidio Ospedaliero Moscati

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Aversa, CE, Italy

Presidio Ospedaliero San Marco Argentano

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San Marco Argentano, CS, Italy

Ospedale Civile "G. Chidichimo"

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Trebisacce, CS, Italy

Ospedale Ignazio Veris Delli Ponti

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Scorrano, LE, Italy

Ospedale Santa Maria degli Ungheresi

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Polistena, RC, Italy

Casa di Cura Madonna della Salute

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Porto Viro, RO, Italy

Ospedale G. Fucito

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Mercato San Severino, SA, Italy

Ospedale Santa Corona

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Pietra Ligure, SV, Italy

Santa Maria della Misericordia

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Udine, UD, Italy

Ospedale Civile San Biagio

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Bovolone, VR, Italy

Ospedale G. Fra Castoro

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San Bonifacio, VR, Italy

Ospedale Valdichiana Santa Margherita

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Cortona, AR, Italy

Ospedale Cardinal Massaia

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Asti, AT, Italy

Azienda Ospedaliera Giuseppe Moscati

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Avellino, AV, Italy

Ospedale Consorziale Policlinico

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Bari, BA, Italy

Ospedale Maggiore

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Bologna, BO, Italy

Ospedale San Giuseppe e Melorio

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Santa Maria Capua Vetere, CE, Italy

Ospedali Civili di Sampierdarena

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Genova-Sampierdarena, GE, Italy

Ospedale Civile Campo di Marte

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Lucca, LU, Italy

Ospedale San Filippo Neri

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Roma, RM, Italy

Ospedale San Camillo

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Roma, RM, Italy

Ospedale Infermi

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Rimini, RN, Italy

Ospedale San Luca

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Vallo della Lucania, SA, Italy

Casa di Cura Villa Bianca

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Trento, TN, Italy

Ospedale Santa Chiara

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Trento, TR, Italy

Azienda Ospedaliera e Universitaria

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Varese, VA, Italy

Ospedale Generale di Zona

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Giugliano in Campania, Italy

Cardiocentro Ticino

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Lugano, Switzerland

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