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

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00376272
• Other study ID #: G106
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2006
• Last updated: April 17, 2009
• Start date: November 2004
• Est. completion date: March 2008

Study information

• Verified date: April 2009
• Source: Gruppo di Ricerca GISSI
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1442
• Est. completion date: March 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Valsartan

• Placebo

Locations

Country	Name	City	State
Italy	Ospedali Riuniti Albano-Genzano	Albano Laziale	RM
Italy	Ospedale Cardinal Massaia	Asti	AT
Italy	Azienda Ospedaliera Giuseppe Moscati	Avellino	AV
Italy	Presidio Ospedaliero Moscati	Aversa	CE
Italy	Ospedale Santa Maria Annunziata	Bagno a Ripoli	FI
Italy	Ospedale Consorziale Policlinico	Bari	BA
Italy	Ospedale di Venere	Bari - Carbonara	BA
Italy	Ospedale di Bentivoglio	Bentivoglio	BO
Italy	Ospedali Riuniti di Bergamo	Bergamo	BG
Italy	Ospedale Bellaria	Bologna	BO
Italy	Ospedale Maggiore	Bologna	BO
Italy	Ospedlae Generale Regionale	Bolzano	BZ
Italy	Ospedale Civile San Biagio	Bovolone	VR
Italy	Casa di Cura Poliambulanza	Brescia	BS
Italy	Azienda Ospedaliera G. Brotzu - S. Michele	Cagliari	CA
Italy	Presidio Ospedaliero F. Ferrari	Casarano	LE
Italy	Azienda Ospedaliera Sant'Anna e San Sebastiano	Caserta	CE
Italy	Ospedale Garibaldi - Nesima	Catania	CT
Italy	Ospedale Civile Pugliese	Catanzaro	CZ
Italy	Ospedale Civile Bassa Val di Cecina	Cecina	LI
Italy	Ospedale Civile Mellini	Chiari	BS
Italy	Ospedale Alta Valle del Tevere	Città di Castello	PG
Italy	Ospedale di Cles	Cles	TN
Italy	Ospedale De Gironcoli	Conegliano Veneto	TV
Italy	Ospedale Santa Maria dei Battuti	Conegliano Veneto	TV
Italy	Ospedale Valdichiana Santa Margherita	Cortona	AR
Italy	Ospedale Santissima Annunziata	Cosenza	CS
Italy	Presidio Ospedaliero Mariano Santo	Cosenza	CS
Italy	Csa di Cura Villa Maria Cecilia	Cotignola	RA
Italy	Ospedlae Maggiore	Crema	CR
Italy	Istituti Ospitalieri di Cremona	Cremona	CR
Italy	Ospedale Civile San Giovanni di Dio	Crotone	KR
Italy	Azienda Ospedaliera Santa Croce e Carle	Cuneo	CN
Italy	Ospedale Generale Provinciale	Este	PD
Italy	Arcispedale Sant'Anna	Ferrara	FE
Italy	Ospedale Civile	Fidenza	PR
Italy	Nuovo Ospedale San Giovanni di Dio	Firenze	FI
Italy	Nuovo Ospedale San Giovanni Battista	Foligno	PG
Italy	Ospedale del dono Svizzero	Formia	LT
Italy	Ospedali Civili di Sampierdarena	Genova-Sampierdarena	GE
Italy	Ospedale San Carlo	Genova-Voltri	GE
Italy	Ospedale Generale di Zona	Giugliano in Campania
Italy	Ospedale Carlo Borella	Giussano	MI
Italy	Ospedale Civile	Imperia	IM
Italy	Ospedale Civile	Lamezia Terme	CZ
Italy	Ospedali Riuniti	Livorno	LI
Italy	Azienda Ospedaliera Mater Domini	Località Germaneto - Catanzaro	CZ
Italy	Ospedale Civile Campo di Marte	Lucca	LU
Italy	Ospedale Madonna delle Grazie	Matera	MT
Italy	Ospedale G. Fucito	Mercato San Severino	SA
Italy	Ospedale Civile Umberto I	Mestre	VE
Italy	Ospedale San Raffaele	Milano	MI
Italy	Ospedale Civile	Milazzo	ME
Italy	Ospedale Civile	Mirano	VE
Italy	Ospedale Policlinico	Modena	MO
Italy	Ospedale Civile San Paolo	Monfalcone	GO
Italy	Azienda Ospedaliera Vincenzo Monaldi	Napoli
Italy	Policlinico Universitario Federico II	Napoli
Italy	Ospedale G. Basilotta	Nicosia	EN
Italy	A.R.N.A.S. Ospedale Civico e Benfratelli	Palermo	PA
Italy	Ospedale Buccheri La Ferla Fatebenefratelli	Palermo	PA
Italy	Ospedale V. Cervello	Palermo	PA
Italy	Presidio Ospedaliero Villa Sofia	Palermo	PA
Italy	Ospedale di Ialmicco - Palmanova - Udine	Palmanova	UD
Italy	Ospedale San Francesco di Paola	Paola	CS
Italy	IRCCS - Fondazione Salvatore Maugeri	Pavia	PV
Italy	Ospedale Policlinico San Matteo IRCCS	Pavia	PV
Italy	Ospedale Civile San Massimo	Penne	PE
Italy	Azienda Ospedaliera San Salvatore	Pesaro	PU
Italy	Ospedale Civile Ave Gratia Plena	Piedimonte Matese	CE
Italy	Ospedale Santa Corona	Pietra Ligure	SV
Italy	Ospedale Civile	Policoro	MT
Italy	Ospedale Santa Maria degli Ungheresi	Polistena	RC
Italy	Azienda Ospedaliera S. Maria degli Angeli	Pordenone	PN
Italy	Casa di Cura Madonna della Salute	Porto Viro	RO
Italy	Ospedale Santa Maria delle Grazie	Pozzuoli
Italy	Policlinico Madonna della Consolazione	Reggio Calabria	RC
Italy	Ospedale Infermi	Rimini	RN
Italy	Ospedale Santa Barbara	Rogliano	CS
Italy	CTO	Roma	RM
Italy	Ospedale San Camillo	Roma	RM
Italy	Ospedale San Camillo	Roma	RM
Italy	Ospedale San Filippo Neri	Roma	RM
Italy	Ospedale San Giovanni	Roma	RM
Italy	Ospedale Sant'Andrea	Roma	RM
Italy	Presidio Ospedaliero	Rovigo	RO
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Ospedale Civile Saluzzo	Saluzzo	CN
Italy	Ospedale G. Fra Castoro	San Bonifacio	VR
Italy	Ospedale S. Antonio	San Daniele del Friuli	UD
Italy	Ospedale Ave Gratia Plena	San Felice a Cancello	CE
Italy	Presidio Ospedaliero San Marco Argentano	San Marco Argentano	CS
Italy	Ospedale San Giuseppe e Melorio	Santa Maria Capua Vetere	CE
Italy	Ospedale San Bartolomeo	Sarzana - Loc. Santa Caterina	SP
Italy	Nuovo Ospedale Civile di Sassuolo	Sassuolo	MO
Italy	Ospedale Scillesi D'America	Scilla	RC
Italy	Ospedale Ignazio Veris Delli Ponti	Scorrano	LE
Italy	Multimedica SPA	Sesto San Giovanni	MI
Italy	Presidio Ospedaliero	Soriano Calabro	VV
Italy	Casa di Cura Villa Verde	Taranto	TA
Italy	Ospedale SS. Annunziata	Taranto	TA
Italy	Ospedale Civile G. Mazzini	Teramo	TE
Italy	Azienda USL 4 Terni	Terni	TR
Italy	Ospedale Evangelico Valdese	Torino	TO
Italy	Ospedale Civile "G. Chidichimo"	Trebisacce	CS
Italy	Casa di Cura Villa Bianca	Trento	TN
Italy	Ospedale Santa Chiara	Trento	TR
Italy	Azienda Ospedaliera - Univ. Ospedali Riuniti	Trieste	TS
Italy	Azienda Servizi Sanitari N. 1 Triestina	Trieste	TS
Italy	Santa Maria della Misericordia	Udine	UD
Italy	Ospedale San Luca	Vallo della Lucania	SA
Italy	Azienda Ospedaliera e Universitaria	Varese	VA
Italy	Ospedale Civile G. Jazzolino	Vibo Valentia	VV
Switzerland	Cardiocentro Ticino	Lugano

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo di Ricerca GISSI

Countries where clinical trial is conducted

Italy,  Switzerland, 

References & Publications (2)

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. — View Citation

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. Erratum in: N Engl J Med. 2009 May 28;360(22):2379. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	First recurrence of AF,		time to first AF recurrence	Yes
Primary	Rate of patients with more than one AF episode,		end of follow-up	No
Secondary	Number of AF episodes		end of fw-up	No
Secondary	Number of hospitalizations for CV reasons		end of fw-up	No
Secondary	Number of all-cause hospitalizations		end of fw-up	No
Secondary	Incidence of thromboembolic events		end of fw-up	No
Secondary	Number of patients who die or with non-fatal thromboembolic events		end of fw-up	No
Secondary	Number of patients in sinus rhythm at the time of each study visit		end of fw-up	No
Secondary	Number of patients in sinus rhythm who did not have any prior AF recurrence during the study		end of fw-up	No
Secondary	Duration and characteristics (ventricular rate) of the first recurrence of AF.		end of fw-up	No

External Links

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