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

Gruppo di Ricerca GISSI

Status and phase: Completed; Phase 3

Conditions: Atrial Fibrillation

Treatments: Drug: Placebo; Drug: Valsartan

Study type: Interventional

Funder types: Other

Identifiers

NCT00376272

G106

Details and patient eligibility

About

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

Full description

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

Enrollment: 1,442 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,442 participants in 2 patient groups, including a placebo group

1

Experimental group

Treatment:

Drug: Valsartan

2

Placebo Comparator group

Treatment:

Drug: Placebo