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 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

Study Type: Interventional

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

Study Primary Completion Date: January 2008

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

Intervention(s) in this Clinical Trial

• Drug: Valsartan
• Drug: Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary 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
    Safety Issue?: Yes
• First recurrence of AF,
  • Time Frame: time to first AF recurrence
    Safety Issue?: Yes
• Rate of patients with more than one AF episode,
  • Time Frame: end of follow-up
    Safety Issue?: No

Secondary Measures

• Number of AF episodes
  • Time Frame: end of fw-up
    Safety Issue?: No
• Number of hospitalizations for CV reasons
  • Time Frame: end of fw-up
    Safety Issue?: No
• Number of all-cause hospitalizations
  • Time Frame: end of fw-up
    Safety Issue?: No
• Incidence of thromboembolic events
  • Time Frame: end of fw-up
    Safety Issue?: No
• Number of patients who die or with non-fatal thromboembolic events
  • Time Frame: end of fw-up
    Safety Issue?: No
• Number of patients in sinus rhythm at the time of each study visit
  • Time Frame: end of fw-up
    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
    Safety Issue?: No
• Duration and characteristics (ventricular rate) of the first recurrence of AF.
  • Time Frame: end of fw-up
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Gruppo di Ricerca GISSI

Overall Clinical Trial Officials and Contacts

Marcello Disertori, MD Study Chair Gruppo di Ricerca GISSI  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00376272

Study ID Number: G106

ClinicalTrials.gov Identifier: NCT00376272

Health Authority: Italy: Ministry of Health