Clinical trial NCT00613496: Irbesartan and Adhesion Molecules in AF
Official title: Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients With Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Persistent Atrial Fibrillation
Keywords: Atrial Fibrillation
irbesartan
AT-II-antagonist
Adhesion Molecules
oxidative stress markers
hsCRP
ICAM
VCAM
MCP-1
vWF
TGFβ1
TNF-α
Interleukin-6
8isoProstaglandinF2α
Lead sponsor: University of Magdeburg
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2008-02-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 22 weeks
Secondary outcomes:
measure: Number of cerebrovascular events
timeFrame: 22 weeks
measure: Number of intermediate medical visits for cardiovascular reasons without hospitalization
timeFrame: 22 weeks
measure: Number of hospitalization for cardiovascular reasons and GFR
timeFrame: 22 weeks
Other outcomes:
Locations:
city: Magdeburg
country: Germany
facility: University Hospital Magdeburg; Div. of Cardiology
Study officials:
affiliation: University Hospital Magdeburg; Div of Cardiology
name: Andreas Goette, MD
role: PRINCIPAL_INVESTIGATOR
References: