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

Condition(s) targeted: Atrial Fibrillation

Intervention: Valsartan (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Gruppo di Ricerca GISSI

Official(s) and/or principal investigator(s):
Marcello Disertori, MD, Study Chair, Affiliation: Gruppo di Ricerca GISSI
Roberto Latini, MD, Study Chair, Affiliation: Gruppo di Ricerca GISSI

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

Official title: Randomized, Prospective, Parallel Group, Placebo-Controlled, Multi-Center Study on the Use of Valsartan an Angiotensin II AT1-Receptor Blocker in the Prevention of Atrial Fibrillation Recurrence

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

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:

First recurrence of AF,

Rate of patients with more than one AF episode,

Secondary outcome:

Number of AF episodes

Number of hospitalizations for CV reasons

Number of all-cause hospitalizations

Incidence of thromboembolic events

Number of patients who die or with non-fatal thromboembolic events

Number of patients in sinus rhythm at the time of each study visit

Number of patients in sinus rhythm who did not have any prior AF recurrence during the study

Duration and characteristics (ventricular rate) of the first recurrence of AF.

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

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Ospedale Santa Chiara, Trento 38100, Italy

Ospedale Evangelico Valdese, Torino 10125, Italy

Azienda Ospedaliera Santa Croce e Carle, Cuneo 12100, Italy

Ospedale Civile Saluzzo, Saluzzo 12037, Italy

Ospedale Cardinal Massaia, Asti 14100, Italy

Azienda Ospedaliera e Universitaria, Varese 21100, Italy

Ospedale Niguarda, Milano 20162, Italy

Ospedale Carlo Borella, Giussano 20034, Italy

Ospedale San Raffaele, Milano 20132, Italy

Ospedali Riuniti di Bergamo, Bergamo 24128, Italy

Ospedale Civile Mellini, Chiari 25032, Italy

Ospedale San Camillo, Roma 00152, Italy

Ospedale Policlinico San Matteo IRCCS, Pavia 27100, Italy

Casa di Cura Poliambulanza, Brescia 25122, Italy

Istituti Ospitalieri di Cremona, Cremona 26100, Italy

Ospedlae Maggiore, Crema 26013, Italy

Istituto Clinico Humanitas, Rozzano 20089, Italy

Multimedica SPA, Sesto San Giovanni 20099, Italy

IRCCS - Fondazione Salvatore Maugeri, Pavia 27100, Italy

Ospedlae Generale Regionale, Bolzano 39100, Italy

Ospedale di Cles, Cles 38023, Italy

Casa di Cura Villa Bianca, Trento 38100, Italy

Ospedale G. Fra Castoro, San Bonifacio 37047, Italy

Ospedale Civile San Biagio, Bovolone 37051, Italy

Ospedale Orlandi, Bussolengo 37012, Italy

Ospedale Santa Maria dei Battuti, Conegliano Veneto 31015, Italy

Ospedale De Gironcoli, Conegliano Veneto 31015, Italy

Ospedale Civile, Mirano 30035, Italy

Ospedale Civile Umberto I, Mestre 30171, Italy

Ospedale Generale Provinciale, Este 35042, Italy

Presidio Ospedaliero, Rovigo 45100, Italy

Casa di Cura Madonna della Salute, Porto Viro 45014, Italy

Santa Maria della Misericordia, Udine 33100, Italy

Ospedale di Ialmicco - Palmanova - Udine, Palmanova 33057, Italy

Ospedale Civile San Paolo, Monfalcone 34072, Italy

Azienda Ospedaliera S. Maria degli Angeli, Pordenone 33170, Italy

Azienda Servizi Sanitari N. 1 Triestina, Trieste 34142, Italy

Ospedale Civile, Imperia 18100, Italy

Ospedale Santa Corona, Pietra Ligure 17027, Italy

Ospedali Civili di Sampierdarena, Genova-Sampierdarena 16149, Italy

Ospedale San Carlo, Genova-Voltri 16158, Italy

Ospedale San Bartolomeo, Sarzana - Loc. Santa Caterina 19038, Italy

Ospedale Civile, Fidenza 43036, Italy

Ospedale Policlinico, Modena 41100, Italy

Nuovo Ospedale Civile di Sassuolo, Sassuolo 41049, Italy

Ospedale di Bentivoglio, Bentivoglio 40010, Italy

Ospedale Maggiore, Bologna 40133, Italy

Ospedale Bellaria, Bologna 40139, Italy

Arcispedale Sant'Anna, Ferrara 44100, Italy

Ospedale Infermi, Rimini 47900, Italy

Csa di Cura Villa Maria Cecilia, Cotignola 48010, Italy

Ospedale Civile Campo di Marte, Lucca 55100, Italy

Nuovo Ospedale San Giovanni di Dio, Firenze 50143, Italy

Ospedale Santa Maria Annunziata, Bagno a Ripoli 50011, Italy

Ospedali Riuniti, Livorno 57124, Italy

Ospedale Civile Bassa Val di Cecina, Cecina 57023, Italy

Ospedale Valdichiana Santa Margherita, Cortona 52040, Italy

Ospedale Alta Valle del Tevere, Città di Castello 06012, Italy

Nuovo Ospedale San Giovanni Battista, Foligno 06034, Italy

Azienda USL 4 Terni, Terni 05100, Italy

Azienda Ospedaliera San Salvatore, Pesaro 61100, Italy

Ospedale S. Antonio, San Daniele del Friuli 33038, Italy

Azienda Ospedaliera - Univ. Ospedali Riuniti, Trieste 34149, Italy

Ospedale San Camillo, Roma 00149, Italy

Ospedale San Giovanni, Roma 00148, Italy

Ospedale San Filippo Neri, Roma 00135, Italy

Ospedali Riuniti Albano-Genzano, Albano Laziale 00041, Italy

CTO, Roma 00145, Italy

Ospedale del dono Svizzero, Formia 04023, Italy

Ospedale Sant'Andrea, Roma 00189, Italy

Ospedale Civile G. Mazzini, Teramo 64100, Italy

Ospedale Civile San Massimo, Penne 65017, Italy

Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta 81100, Italy

Ospedale San Giuseppe e Melorio, Santa Maria Capua Vetere 81055, Italy

Ospedale Civile Ave Gratia Plena, Piedimonte Matese 81016, Italy

Ospedale Ave Gratia Plena, San Felice a Cancello 81027, Italy

Presidio Ospedaliero Moscati, Aversa 81031, Italy

Policlinico Universitario Federico II, Napoli 80131, Italy

Ospedale Generale di Zona, Giugliano in Campania 80014, Italy

Azienda Ospedaliera Vincenzo Monaldi, Napoli 80131, Italy

Azienda Ospedaliera Giuseppe Moscati, Avellino 83100, Italy

Ospedale San Luca, Vallo della Lucania 84078, Italy

Ospedale G. Fucito, Mercato San Severino 84085, Italy

Ospedale Santa Maria delle Grazie, Pozzuoli 80078, Italy

Ospedale Consorziale Policlinico, Bari 70124, Italy

Ospedale di Venere, Bari - Carbonara 70012, Italy

Presidio Ospedaliero F. Ferrari, Casarano 73042, Italy

Ospedale Ignazio Veris Delli Ponti, Scorrano 73020, Italy

Ospedale SS. Annunziata, Taranto 74100, Italy

Casa di Cura Villa Verde, Taranto 74100, Italy

Ospedale Madonna delle Grazie, Matera 75100, Italy

Ospedale Civile, Policoro 75025, Italy

Ospedale Santissima Annunziata, Cosenza 87100, Italy

Presidio Ospedaliero Mariano Santo, Cosenza 87100, Italy

Ospedale San Francesco di Paola, Paola 87027, Italy

Ospedale Santa Barbara, Rogliano 87054, Italy

Ospedale Civile "G. Chidichimo", Trebisacce 87075, Italy

Ospedale Civile Pugliese, Catanzaro 88100, Italy

Ospedale Civile San Giovanni di Dio, Crotone 88900, Italy

Ospedale Civile, Lamezia Terme 88046, Italy

Ospedale Civile G. Jazzolino, Vibo Valentia 89900, Italy

Presidio Ospedaliero, Soriano Calabro 89831, Italy

Ospedale Santa Maria degli Ungheresi, Polistena 89024, Italy

Ospedale Scillesi D'America, Scilla 89024, Italy

Policlinico Madonna della Consolazione, Reggio Calabria 89124, Italy

Presidio Ospedaliero San Marco Argentano, San Marco Argentano 87018, Italy

Azienda Ospedaliera Mater Domini, Località Germaneto - Catanzaro 88100, Italy

Ospedale G. Basilotta, Nicosia 94014, Italy

Ospedale Civile, Milazzo 98057, Italy

A.R.N.A.S. Ospedale Civico e Benfratelli, Palermo 90127, Italy

Ospedale V. Cervello, Palermo 90146, Italy

Presidio Ospedaliero Villa Sofia, Palermo 90146, Italy

Ospedale Buccheri La Ferla Fatebenefratelli, Palermo 90123, Italy

Ospedale Garibaldi - Nesima, Catania 95122, Italy

Azienda Ospedaliera G. Brotzu - S. Michele, Cagliari 09134, Italy

Cardiocentro Ticino, Lugano 69000, Switzerland

Related publications:

Disertori M, Latini R, Maggioni AP, Delise P, Di Pasquale G, Franzosi MG, Staszewsky L, Tognoni G; GISSI-AF Investigators. Rationale and design of the GISSI-Atrial Fibrillation Trial: a randomized, prospective, multicentre study on the use of valsartan, an angiotensin II AT1-receptor blocker, in the prevention of atrial fibrillation recurrence. J Cardiovasc Med (Hagerstown). 2006 Jan;7(1):29-38.

Starting date: November 2004
Ending date: March 2008
Last updated: May 23, 2008