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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376272

  Show 114 Study Locations
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
Angiotensin II
Valsartan
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on July 22, 2014