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

This study has been completed.
Sponsor:
Information provided by:
Gruppo di Ricerca GISSI
ClinicalTrials.gov Identifier:
NCT00376272
First received: September 12, 2006
Last updated: April 17, 2009
Last verified: April 2009
  Purpose

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

Condition Intervention Phase
Atrial Fibrillation
Drug: Valsartan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gruppo di Ricerca GISSI:

Primary Outcome Measures:
  • 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 Frame: Time to first AF recurrence ] [ Designated as safety issue: Yes ]
  • First recurrence of AF, [ Time Frame: time to first AF recurrence ] [ Designated as safety issue: Yes ]
  • Rate of patients with more than one AF episode, [ Time Frame: end of follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of AF episodes [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Number of hospitalizations for CV reasons [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Number of all-cause hospitalizations [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Incidence of thromboembolic events [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Number of patients who die or with non-fatal thromboembolic events [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Number of patients in sinus rhythm at the time of each study visit [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Number of patients in sinus rhythm who did not have any prior AF recurrence during the study [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]
  • Duration and characteristics (ventricular rate) of the first recurrence of AF. [ Time Frame: end of fw-up ] [ Designated as safety issue: No ]

Enrollment: 1442
Study Start Date: November 2004
Study Completion Date: March 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Valsartan
Placebo Comparator: 2 Drug: Placebo

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00376272

  Hide Study Locations
Locations
Italy
Ospedale Valdichiana Santa Margherita
Cortona, AR, Italy, 52040
Ospedale Cardinal Massaia
Asti, AT, Italy, 14100
Azienda Ospedaliera Giuseppe Moscati
Avellino, AV, Italy, 83100
Ospedale Consorziale Policlinico
Bari, BA, Italy, 70124
Ospedale di Venere
Bari - Carbonara, BA, Italy, 70012
Ospedali Riuniti di Bergamo
Bergamo, BG, Italy, 24128
Ospedale di Bentivoglio
Bentivoglio, BO, Italy, 40010
Ospedale Maggiore
Bologna, BO, Italy, 40133
Ospedale Bellaria
Bologna, BO, Italy, 40139
Casa di Cura Poliambulanza
Brescia, BS, Italy, 25122
Ospedale Civile Mellini
Chiari, BS, Italy, 25032
Ospedlae Generale Regionale
Bolzano, BZ, Italy, 39100
Azienda Ospedaliera G. Brotzu - S. Michele
Cagliari, CA, Italy, 09134
Presidio Ospedaliero Moscati
Aversa, CE, Italy, 81031
Azienda Ospedaliera Sant'Anna e San Sebastiano
Caserta, CE, Italy, 81100
Ospedale Civile Ave Gratia Plena
Piedimonte Matese, CE, Italy, 81016
Ospedale Ave Gratia Plena
San Felice a Cancello, CE, Italy, 81027
Ospedale San Giuseppe e Melorio
Santa Maria Capua Vetere, CE, Italy, 81055
Azienda Ospedaliera Santa Croce e Carle
Cuneo, CN, Italy, 12100
Ospedale Civile Saluzzo
Saluzzo, CN, Italy, 12037
Ospedlae Maggiore
Crema, CR, Italy, 26013
Istituti Ospitalieri di Cremona
Cremona, CR, Italy, 26100
Ospedale Santissima Annunziata
Cosenza, CS, Italy, 87100
Presidio Ospedaliero Mariano Santo
Cosenza, CS, Italy, 87100
Ospedale San Francesco di Paola
Paola, CS, Italy, 87027
Ospedale Santa Barbara
Rogliano, CS, Italy, 87054
Presidio Ospedaliero San Marco Argentano
San Marco Argentano, CS, Italy, 87018
Ospedale Civile "G. Chidichimo"
Trebisacce, CS, Italy, 87075
Ospedale Garibaldi - Nesima
Catania, CT, Italy, 95122
Ospedale Civile Pugliese
Catanzaro, CZ, Italy, 88100
Ospedale Civile
Lamezia Terme, CZ, Italy, 88046
Azienda Ospedaliera Mater Domini
Località Germaneto - Catanzaro, CZ, Italy, 88100
Ospedale G. Basilotta
Nicosia, EN, Italy, 94014
Arcispedale Sant'Anna
Ferrara, FE, Italy, 44100
Ospedale Santa Maria Annunziata
Bagno a Ripoli, FI, Italy, 50011
Nuovo Ospedale San Giovanni di Dio
Firenze, FI, Italy, 50143
Ospedali Civili di Sampierdarena
Genova-Sampierdarena, GE, Italy, 16149
Ospedale San Carlo
Genova-Voltri, GE, Italy, 16158
Ospedale Civile San Paolo
Monfalcone, GO, Italy, 34072
Ospedale Civile
Imperia, IM, Italy, 18100
Ospedale Civile San Giovanni di Dio
Crotone, KR, Italy, 88900
Presidio Ospedaliero F. Ferrari
Casarano, LE, Italy, 73042
Ospedale Ignazio Veris Delli Ponti
Scorrano, LE, Italy, 73020
Ospedale Civile Bassa Val di Cecina
Cecina, LI, Italy, 57023
Ospedali Riuniti
Livorno, LI, Italy, 57124
Ospedale del dono Svizzero
Formia, LT, Italy, 04023
Ospedale Civile Campo di Marte
Lucca, LU, Italy, 55100
Ospedale Civile
Milazzo, ME, Italy, 98057
Ospedale Carlo Borella
Giussano, MI, Italy, 20034
Ospedale San Raffaele
Milano, MI, Italy, 20132
Istituto Clinico Humanitas
Rozzano, MI, Italy, 20089
Multimedica SPA
Sesto San Giovanni, MI, Italy, 20099
Ospedale Policlinico
Modena, MO, Italy, 41100
Nuovo Ospedale Civile di Sassuolo
Sassuolo, MO, Italy, 41049
Ospedale Madonna delle Grazie
Matera, MT, Italy, 75100
Ospedale Civile
Policoro, MT, Italy, 75025
Presidio Ospedaliero Villa Sofia
Palermo, PA, Italy, 90146
Ospedale Buccheri La Ferla Fatebenefratelli
Palermo, PA, Italy, 90123
A.R.N.A.S. Ospedale Civico e Benfratelli
Palermo, PA, Italy, 90127
Ospedale V. Cervello
Palermo, PA, Italy, 90146
Ospedale Generale Provinciale
Este, PD, Italy, 35042
Ospedale Civile San Massimo
Penne, PE, Italy, 65017
Ospedale Alta Valle del Tevere
Città di Castello, PG, Italy, 06012
Nuovo Ospedale San Giovanni Battista
Foligno, PG, Italy, 06034
Azienda Ospedaliera S. Maria degli Angeli
Pordenone, PN, Italy, 33170
Ospedale Civile
Fidenza, PR, Italy, 43036
Azienda Ospedaliera San Salvatore
Pesaro, PU, Italy, 61100
IRCCS - Fondazione Salvatore Maugeri
Pavia, PV, Italy, 27100
Ospedale Policlinico San Matteo IRCCS
Pavia, PV, Italy, 27100
Csa di Cura Villa Maria Cecilia
Cotignola, RA, Italy, 48010
Ospedale Santa Maria degli Ungheresi
Polistena, RC, Italy, 89024
Policlinico Madonna della Consolazione
Reggio Calabria, RC, Italy, 89124
Ospedale Scillesi D'America
Scilla, RC, Italy, 89024
Ospedali Riuniti Albano-Genzano
Albano Laziale, RM, Italy, 00041
Ospedale San Giovanni
Roma, RM, Italy, 00148
Ospedale Sant'Andrea
Roma, RM, Italy, 00189
Ospedale San Filippo Neri
Roma, RM, Italy, 00135
CTO
Roma, RM, Italy, 00145
Ospedale San Camillo
Roma, RM, Italy, 00149
Ospedale San Camillo
Roma, RM, Italy, 00152
Ospedale Infermi
Rimini, RN, Italy, 47900
Casa di Cura Madonna della Salute
Porto Viro, RO, Italy, 45014
Presidio Ospedaliero
Rovigo, RO, Italy, 45100
Ospedale G. Fucito
Mercato San Severino, SA, Italy, 84085
Ospedale San Luca
Vallo della Lucania, SA, Italy, 84078
Ospedale San Bartolomeo
Sarzana - Loc. Santa Caterina, SP, Italy, 19038
Ospedale Santa Corona
Pietra Ligure, SV, Italy, 17027
Casa di Cura Villa Verde
Taranto, TA, Italy, 74100
Ospedale SS. Annunziata
Taranto, TA, Italy, 74100
Ospedale Civile G. Mazzini
Teramo, TE, Italy, 64100
Ospedale di Cles
Cles, TN, Italy, 38023
Casa di Cura Villa Bianca
Trento, TN, Italy, 38100
Ospedale Evangelico Valdese
Torino, TO, Italy, 10125
Azienda USL 4 Terni
Terni, TR, Italy, 05100
Ospedale Santa Chiara
Trento, TR, Italy, 38100
Azienda Ospedaliera - Univ. Ospedali Riuniti
Trieste, TS, Italy, 34149
Azienda Servizi Sanitari N. 1 Triestina
Trieste, TS, Italy, 34142
Ospedale De Gironcoli
Conegliano Veneto, TV, Italy, 31015
Ospedale Santa Maria dei Battuti
Conegliano Veneto, TV, Italy, 31015
Ospedale di Ialmicco - Palmanova - Udine
Palmanova, UD, Italy, 33057
Ospedale S. Antonio
San Daniele del Friuli, UD, Italy, 33038
Santa Maria della Misericordia
Udine, UD, Italy, 33100
Azienda Ospedaliera e Universitaria
Varese, VA, Italy, 21100
Ospedale Civile Umberto I
Mestre, VE, Italy, 30171
Ospedale Civile
Mirano, VE, Italy, 30035
Ospedale Civile San Biagio
Bovolone, VR, Italy, 37051
Ospedale G. Fra Castoro
San Bonifacio, VR, Italy, 37047
Presidio Ospedaliero
Soriano Calabro, VV, Italy, 89831
Ospedale Civile G. Jazzolino
Vibo Valentia, VV, Italy, 89900
Ospedale Generale di Zona
Giugliano in Campania, Italy, 80014
Policlinico Universitario Federico II
Napoli, Italy, 80131
Azienda Ospedaliera Vincenzo Monaldi
Napoli, Italy, 80131
Ospedale Santa Maria delle Grazie
Pozzuoli, Italy, 80078
Switzerland
Cardiocentro Ticino
Lugano, Switzerland, 6900
Sponsors and Collaborators
Gruppo di Ricerca GISSI
Investigators
Study Chair: Marcello Disertori, MD Gruppo di Ricerca GISSI
Study Chair: Roberto Latini, MD Gruppo di Ricerca GISSI
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Aldo P. Maggioni, Heart Care Foundation
ClinicalTrials.gov Identifier: NCT00376272     History of Changes
Other Study ID Numbers: G106
Study First Received: September 12, 2006
Last Updated: April 17, 2009
Health Authority: Italy: Ministry of Health

Keywords provided by Gruppo di Ricerca GISSI:
atrial fibrillation,atrial remodeling,dysrhythmias,valsartan

Additional relevant MeSH terms:
Atrial Fibrillation
Recurrence
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Disease Attributes
Valsartan
Angiotensin II
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on September 22, 2014