Official Title: “Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients With Persistent Atrial Fibrillation”

Experimental data suggest that angiotensin II-antagonists reduce the atrial expression of prothrombotic adhesion molecules and oxidative stress parameters. The present study is designed to investigate the effects on angiotensin II-antagonist irbesartan to reduce the amounts of circulating oxidative stress markers and adhesion molecules in patients with persistent atrial fibrillation.

Study Type: Interventional

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

Study Primary Completion Date: March 2009

Primary Objective:

The aim of the study is to assess that blocking the angiotensin II type 1 receptor reduces systemic levels of oxidative stress markers and adhesion molecules by more than 25% compared to placebo in patients with persistent/permanent atrial fibrillation.

Primary Target Parameter:

The primary target parameter is defined as reduction of systemic levels of oxidative stress markers and adhesion molecules (hsCRP, ICAM, VCAM, MCP-1, vWF, TGFβ1, TNF-α, Interleukin-6, 8isoProstaglandinF2α)

Secondary Target Parameter:

The secondary Target Parameters are defined as number of cerebrovascular events, number of intermediate medical visits for cardiovascular reasons without hospitalisation, number of hospitalisations for cardiovascular reasons and GFR.

Intervention(s) in this Clinical Trial

• Drug: irbesartan
  • Irbesartan-tablet (150 mg) 1 in the morning for 7 days, 2 tablets (1 in the morning and 1 in the evening) after day 8 if no contraindication for up titration (investigator will decide on the basis of creatinin, urea and potassium after taking a blood sample) for 9 weeks.
• Drug: placebo
  • Placebo-tablet, 1 in the morning for 7 days, 2 tablets (1 in the morning and 1 in the evening) after day 8.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 2
  • Placebo treatment in each patient during the study (9 weeks) using an intraindividual cross-over design
• Active Comparator: 1
  • Irbesartan treatment in each patient during the study (9 weeks) using an intraindividual cross-over design

Primary Measures

• The primary target parameter is defined as reduction of systemic levels of oxidative stress markers and adhesion molecules (hsCRP, ICAM, VCAM, MCP-1, vWF, TGFβ1, TNF-α, Interleukin-6, 8isoProstaglandinF2α)
  • Time Frame: 22 weeks
    Safety Issue?: No

Secondary Measures

• Number of cerebrovascular events
  • Time Frame: 22 weeks
    Safety Issue?: No
• Number of intermediate medical visits for cardiovascular reasons without hospitalization
  • Time Frame: 22 weeks
    Safety Issue?: No
• Number of hospitalization for cardiovascular reasons and GFR
  • Time Frame: 22 weeks
    Safety Issue?: No

Inclusion Criteria:

• Patients with persistent/permanent AF (>2 months)
• CHADS2 Score ≥2
• Age ≥18
• Patient informed orally and in writing
• Written informed consent of the patient
• Patients who are anticipated to show sufficient compliance in following the study protocol
• Patients must agree to undergo the 148 days clinical follow-up
• Patients who are mentally and linguistically able to understand the aim of the study and the associated risks and benefits of the treatment. The patients, by providing informed consent, agree to this treatment as stated in the patient informed consent document.

Exclusion Criteria:

• Strong clinical evidence that prevents the temporary pause of therapy with AT II antagonists
• Symptomatic bradycardia
• Implanted pacemaker or implanted cardioverter/defibrillator with any antitachycardia algorithm in use
• Cardiac surgery or cardiac catheter ablation within the last 3 months prior to randomisation
• Typical angina pectoris symptoms at rest or during exercise
• Known coronary artery disease with indication for intervention
• Symptomatic peripheral vascular disease
• Left ventricular ejection fraction <35%
• Myocardial infarction within 6 months prior to randomisation
• Diastolic blood pressure >110mmHg at rest
• Symptomatic arterial hypotension
• Known renal artery stenosis
• Serum creatinin >1.8mval/l
• Chronic inflammatory disease
• Acute inflammatory disease (CRP >20mg/L)
• Relevant hepatic or pulmonary disorders
• Hyperthyreosis manifested clinically and in laboratory
• Known drug intolerance for AT II inhibitors
• Females who are pregnant or breast feeding
• Females of childbearing potential who are not using a scientifically accepted method of contraception
• Participation in a clinical trial within the last 30 days prior to randomisation
• Drug addiction or chronic alcohol abuse
• Cancer or other disease, which inevitably leads to death
• Legal incapacity, or other circumstances which would prevent the patient from understanding the aim, nature or extent of the clinical study, evidence of an uncooperative attitude

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Magdeburg

Overall Clinical Trial Officials and Contacts

Andreas Goette, MD Principal Investigator University Hospital Magdeburg; Div of Cardiology  

Overall Contact: Andreas Goette, MD 00493916713225 andreas.goette@medizin.uni-magdeburg.de

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00613496

Study ID Number: AG-1-2007

ClinicalTrials.gov Identifier: NCT00613496

Health Authority: Germany: Federal Institute for Drugs and Medical Devices