NCT00376272

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,442

participants targeted

Target at P75+ for phase_3 atrial-fibrillation

Timeline
Completed

Started Nov 2004

Typical duration for phase_3 atrial-fibrillation

Geographic Reach
2 countries

114 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2004

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

September 12, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 14, 2006

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2008

Completed
Last Updated

April 20, 2009

Status Verified

April 1, 2009

Enrollment Period

3.2 years

First QC Date

September 12, 2006

Last Update Submit

April 17, 2009

Conditions

Keywords

atrial fibrillation,atrial remodeling,dysrhythmias,valsartan

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (8)

  • Number of AF episodes

    end of fw-up

  • Number of hospitalizations for CV reasons

    end of fw-up

  • Number of all-cause hospitalizations

    end of fw-up

  • Incidence of thromboembolic events

    end of fw-up

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

    end of fw-up

  • +3 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL
Drug: Valsartan

2

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients \>=40 years of age
  • Sinus rhythm
  • 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
  • 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)
  • Written informed consent to participate in the study prior to any study procedures

You may not qualify if:

  • Need for a continuous treatment with ARBs for any clinical reasons
  • Contraindications or known hypersensitivity to ARBs
  • Persistent standing systolic blood pressure \< 110 mmHg
  • Recent (\<6 weeks) acute myocardial infarction or bypass surgery, or percutaneous coronary intervention
  • Clinically significant valvular etiologies
  • Thyroid dysfunction
  • Indication for pacemaker or ICD implant or for an ablative treatment, recent (\<6 months) PM or ICD implant, previous ablative treatment
  • Planned cardiac surgery, expected to be performed within 3 months
  • Serum creatinine level above 2.5 mg/dL
  • Significant liver disease
  • Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception
  • 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
  • Presence of any non-cardiac disease (e.g. cancer) that is likely to significantly shorten life expectancy
  • Treatment with any investigational agent within 1 month before randomization
  • Currently decompensated heart failure

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (114)

Ospedale Valdichiana Santa Margherita

Cortona, AR, 52040, Italy

Location

Ospedale Cardinal Massaia

Asti, AT, 14100, Italy

Location

Azienda Ospedaliera Giuseppe Moscati

Avellino, AV, 83100, Italy

Location

Ospedale Consorziale Policlinico

Bari, BA, 70124, Italy

Location

Ospedale di Venere

Bari - Carbonara, BA, 70012, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, BG, 24128, Italy

Location

Ospedale di Bentivoglio

Bentivoglio, BO, 40010, Italy

Location

Ospedale Maggiore

Bologna, BO, 40133, Italy

Location

Ospedale Bellaria

Bologna, BO, 40139, Italy

Location

Casa di Cura Poliambulanza

Brescia, BS, 25122, Italy

Location

Ospedale Civile Mellini

Chiari, BS, 25032, Italy

Location

Ospedlae Generale Regionale

Bolzano, BZ, 39100, Italy

Location

Azienda Ospedaliera G. Brotzu - S. Michele

Cagliari, CA, 09134, Italy

Location

Presidio Ospedaliero Moscati

Aversa, CE, 81031, Italy

Location

Azienda Ospedaliera Sant'Anna e San Sebastiano

Caserta, CE, 81100, Italy

Location

Ospedale Civile Ave Gratia Plena

Piedimonte Matese, CE, 81016, Italy

Location

Ospedale Ave Gratia Plena

San Felice A Cancello, CE, 81027, Italy

Location

Ospedale San Giuseppe e Melorio

Santa Maria Capua Vetere, CE, 81055, Italy

Location

Azienda Ospedaliera Santa Croce e Carle

Cuneo, CN, 12100, Italy

Location

Ospedale Civile Saluzzo

Saluzzo, CN, 12037, Italy

Location

Ospedlae Maggiore

Crema, CR, 26013, Italy

Location

Istituti Ospitalieri di Cremona

Cremona, CR, 26100, Italy

Location

Ospedale Santissima Annunziata

Cosenza, CS, 87100, Italy

Location

Presidio Ospedaliero Mariano Santo

Cosenza, CS, 87100, Italy

Location

Ospedale San Francesco di Paola

Paola, CS, 87027, Italy

Location

Ospedale Santa Barbara

Rogliano, CS, 87054, Italy

Location

Presidio Ospedaliero San Marco Argentano

San Marco Argentano, CS, 87018, Italy

Location

Ospedale Civile "G. Chidichimo"

Trebisacce, CS, 87075, Italy

Location

Ospedale Garibaldi - Nesima

Catania, CT, 95122, Italy

Location

Ospedale Civile Pugliese

Catanzaro, CZ, 88100, Italy

Location

Ospedale Civile

Lamezia Terme, CZ, 88046, Italy

Location

Azienda Ospedaliera Mater Domini

LocalitĂ  Germaneto - Catanzaro, CZ, 88100, Italy

Location

Ospedale G. Basilotta

Nicosia, EN, 94014, Italy

Location

Arcispedale Sant'Anna

Ferrara, FE, 44100, Italy

Location

Ospedale Santa Maria Annunziata

Bagno a Ripoli, FI, 50011, Italy

Location

Nuovo Ospedale San Giovanni di Dio

Florence, FI, 50143, Italy

Location

Ospedali Civili di Sampierdarena

Genova-Sampierdarena, GE, 16149, Italy

Location

Ospedale San Carlo

Genova-Voltri, GE, 16158, Italy

Location

Ospedale Civile San Paolo

Monfalcone, GO, 34072, Italy

Location

Ospedale Civile

Imperia, IM, 18100, Italy

Location

Ospedale Civile San Giovanni di Dio

Crotone, KR, 88900, Italy

Location

Presidio Ospedaliero F. Ferrari

Casarano, LE, 73042, Italy

Location

Ospedale Ignazio Veris Delli Ponti

Scorrano, LE, 73020, Italy

Location

Ospedale Civile Bassa Val di Cecina

Cecina, LI, 57023, Italy

Location

Ospedali Riuniti

Livorno, LI, 57124, Italy

Location

Ospedale del dono Svizzero

Formia, LT, 04023, Italy

Location

Ospedale Civile Campo di Marte

Lucca, LU, 55100, Italy

Location

Ospedale Civile

Milazzo, ME, 98057, Italy

Location

Ospedale Carlo Borella

Giussano, MI, 20034, Italy

Location

Ospedale San Raffaele

Milan, MI, 20132, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Multimedica SPA

Sesto San Giovanni, MI, 20099, Italy

Location

Ospedale Policlinico

Modena, MO, 41100, Italy

Location

Nuovo Ospedale Civile di Sassuolo

Sassuolo, MO, 41049, Italy

Location

Ospedale Madonna delle Grazie

Matera, MT, 75100, Italy

Location

Ospedale Civile

Policoro, MT, 75025, Italy

Location

Ospedale Buccheri La Ferla Fatebenefratelli

Palermo, PA, 90123, Italy

Location

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

Palermo, PA, 90127, Italy

Location

Ospedale V. Cervello

Palermo, PA, 90146, Italy

Location

Presidio Ospedaliero Villa Sofia

Palermo, PA, 90146, Italy

Location

Ospedale Generale Provinciale

Este, PD, 35042, Italy

Location

Ospedale Civile San Massimo

Penne, PE, 65017, Italy

Location

Ospedale Alta Valle del Tevere

CittĂ  di Castello, PG, 06012, Italy

Location

Nuovo Ospedale San Giovanni Battista

Foligno, PG, 06034, Italy

Location

Azienda Ospedaliera S. Maria degli Angeli

Pordenone, PN, 33170, Italy

Location

Ospedale Civile

Fidenza, PR, 43036, Italy

Location

Azienda Ospedaliera San Salvatore

Pesaro, PU, 61100, Italy

Location

IRCCS - Fondazione Salvatore Maugeri

Pavia, PV, 27100, Italy

Location

Ospedale Policlinico San Matteo IRCCS

Pavia, PV, 27100, Italy

Location

Csa di Cura Villa Maria Cecilia

Cotignola, RA, 48010, Italy

Location

Ospedale Santa Maria degli Ungheresi

Polistena, RC, 89024, Italy

Location

Policlinico Madonna della Consolazione

Reggio Calabria, RC, 89124, Italy

Location

Ospedale Scillesi D'America

Scilla, RC, 89024, Italy

Location

Ospedali Riuniti Albano-Genzano

Albano Laziale, RM, 00041, Italy

Location

Ospedale San Filippo Neri

Roma, RM, 00135, Italy

Location

CTO

Roma, RM, 00145, Italy

Location

Ospedale San Giovanni

Roma, RM, 00148, Italy

Location

Ospedale San Camillo

Roma, RM, 00149, Italy

Location

Ospedale San Camillo

Roma, RM, 00152, Italy

Location

Ospedale Sant'Andrea

Roma, RM, 00189, Italy

Location

Ospedale Infermi

Rimini, RN, 47900, Italy

Location

Casa di Cura Madonna della Salute

Porto Viro, RO, 45014, Italy

Location

Presidio Ospedaliero

Rovigo, RO, 45100, Italy

Location

Ospedale G. Fucito

Mercato San Severino, SA, 84085, Italy

Location

Ospedale San Luca

Vallo della Lucania, SA, 84078, Italy

Location

Ospedale San Bartolomeo

Sarzana - Loc. Santa Caterina, SP, 19038, Italy

Location

Ospedale Santa Corona

Pietra Ligure, SV, 17027, Italy

Location

Casa di Cura Villa Verde

Taranto, TA, 74100, Italy

Location

Ospedale SS. Annunziata

Taranto, TA, 74100, Italy

Location

Ospedale Civile G. Mazzini

Teramo, TE, 64100, Italy

Location

Ospedale di Cles

Cles, TN, 38023, Italy

Location

Casa di Cura Villa Bianca

Trento, TN, 38100, Italy

Location

Ospedale Evangelico Valdese

Torino, TO, 10125, Italy

Location

Azienda USL 4 Terni

Terni, TR, 05100, Italy

Location

Ospedale Santa Chiara

Trento, TR, 38100, Italy

Location

Azienda Servizi Sanitari N. 1 Triestina

Trieste, TS, 34142, Italy

Location

Azienda Ospedaliera - Univ. Ospedali Riuniti

Trieste, TS, 34149, Italy

Location

Ospedale De Gironcoli

Conegliano Veneto, TV, 31015, Italy

Location

Ospedale Santa Maria dei Battuti

Conegliano Veneto, TV, 31015, Italy

Location

Ospedale di Ialmicco - Palmanova - Udine

Palmanova, UD, 33057, Italy

Location

Ospedale S. Antonio

San Daniele del Friuli, UD, 33038, Italy

Location

Santa Maria della Misericordia

Udine, UD, 33100, Italy

Location

Azienda Ospedaliera e Universitaria

Varese, VA, 21100, Italy

Location

Ospedale Civile Umberto I

Mestre, VE, 30171, Italy

Location

Ospedale Civile

Mirano, VE, 30035, Italy

Location

Ospedale Civile San Biagio

Bovolone, VR, 37051, Italy

Location

Ospedale G. Fra Castoro

San Bonifacio, VR, 37047, Italy

Location

Presidio Ospedaliero

Soriano Calabro, VV, 89831, Italy

Location

Ospedale Civile G. Jazzolino

Vibo Valentia, VV, 89900, Italy

Location

Ospedale Generale di Zona

Giugliano in Campania, 80014, Italy

Location

Azienda Ospedaliera Vincenzo Monaldi

Napoli, 80131, Italy

Location

Policlinico Universitario Federico II

Napoli, 80131, Italy

Location

Ospedale Santa Maria delle Grazie

Pozzuoli, 80078, Italy

Location

Cardiocentro Ticino

Lugano, 6900, Switzerland

Location

Related Publications (6)

  • 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. doi: 10.2459/01.JCM.0000199778.85343.08.

    PMID: 16645357BACKGROUND
  • GISSI-AF Investigators; Disertori M, Latini R, Barlera S, Franzosi MG, Staszewsky L, Maggioni AP, Lucci D, Di Pasquale G, Tognoni G. Valsartan for prevention of recurrent atrial fibrillation. N Engl J Med. 2009 Apr 16;360(16):1606-17. doi: 10.1056/NEJMoa0805710.

    PMID: 19369667BACKGROUND
  • Disertori M, Franzosi MG, Barlera S, Cosmi F, Quintarelli S, Favero C, Cappellini G, Fabbri G, Maggioni AP, Staszewsky L, Moroni LA, Latini R; GISSI-AF investigators. Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: data from the GISSI-AF trial. BMC Cardiovasc Disord. 2013 Apr 15;13:28. doi: 10.1186/1471-2261-13-28.

  • Staszewsky L, Wong M, Masson S, Raimondi E, Gramenzi S, Proietti G, Bicego D, Emanuelli C, Pulitano G, Taddei F, Nicolis EB, Correale E, Fabbri G, Bertocchi F, Franzosi MG, Maggioni AP, Tognoni G, Disertori M, Latini R; GISSI-AF Investigators. Left atrial remodeling and response to valsartan in the prevention of recurrent atrial fibrillation: the GISSI-AF echocardiographic substudy. Circ Cardiovasc Imaging. 2011 Nov;4(6):721-8. doi: 10.1161/CIRCIMAGING.111.965954. Epub 2011 Sep 16.

  • Disertori M, Lombardi F, Barlera S, Maggioni AP, Favero C, Franzosi MG, Lucci D, Staszewsky L, Fabbri G, Quintarelli S, Bianconi L, Latini R. Clinical characteristics of patients with asymptomatic recurrences of atrial fibrillation in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial. Am Heart J. 2011 Aug;162(2):382-9. doi: 10.1016/j.ahj.2011.05.008. Epub 2011 Jul 7.

  • Disertori M, Lombardi F, Barlera S, Latini R, Maggioni AP, Zeni P, Di Pasquale G, Cosmi F, Franzosi MG; GISSI-AF Investigators. Clinical predictors of atrial fibrillation recurrence in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial. Am Heart J. 2010 May;159(5):857-63. doi: 10.1016/j.ahj.2010.02.016.

Related Links

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Valsartan

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsValineAmino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Study Officials

  • Marcello Disertori, MD

    Gruppo di Ricerca GISSI

    STUDY CHAIR
  • Roberto Latini, MD

    Gruppo di Ricerca GISSI

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 12, 2006

First Posted

September 14, 2006

Study Start

November 1, 2004

Primary Completion

January 1, 2008

Study Completion

March 1, 2008

Last Updated

April 20, 2009

Record last verified: 2009-04

Locations