title: Rationale for and design of the CREATIVE-AF trial: randomized, double-blind, placebo-controlled, crossover study of the effect of irbesartan on oxidative stress and adhesion molecules in patients with persistent atrial fibrillation.
abstract: OBJECTIVE
  Atrial fibrillation (AF) is the most common cardiac arrhythmia. Recent studies suggest there is an angiotensin II-dependent increase in adhesion molecules and oxidative stress parameters during AF. These alterations appear to contribute to inflammatory and prothrombotic changes in the atrial endocardium ('endocardial remodelling'), suggesting that patients with increased levels of these factors might be at risk of thromboembolic events. The purpose of the CREATIVE-AF (Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients with Persistent Atrial Fibrillation) trial is to prove the principle concept that blockade of angiotensin II type 1 receptors by irbesartan reduces levels of circulating adhesion molecules and oxidative stress parameters in patients with persistent AF by 25% compared with placebo.
  
  
  METHODS
  This is a prospective, randomized, double-blind, placebo-controlled, crossover study in patients with persistent/permanent AF. A total of 60 patients are planned to be included in the study. Patients will receive placebo and irbesartan therapy for 9 weeks each. Levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), inflammatory markers (high sensitivity C-reactive protein, monocyte chemoattractant protein-1, von Willebrand factor, tumour growth factor-beta1, tumour necrosis factor-alpha, interleukin-6) and oxidative stress parameters (8-iso-prostaglandin F2alpha) will be determined after each treatment phase and compared with baseline levels.
  
  
  CONCLUSIONS
  Angiotensin II type 1 receptor antagonists may help reduce levels of circulating adhesion molecules and oxidative stress parameters in patients with persistent AF. This article summarizes the rationale and design of the CREATIVE-AF trial, which has been designed to test this hypothesis.
authors.affiliation: Department of Cardiology, Otto-von-Guericke-University Hospital, Magdeburg, Germany. andreas.goette@med.ovgu.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Alessandro
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.forename: Christian
authors.initials: C
authors.lastname: Mewis
authors.forename: Christoph
authors.initials: C
authors.lastname: Stellbrink
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tebbenjohanns
authors.forename: Christian
authors.initials: C
authors.lastname: Weiss
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D018579:Patient Selection; D018401:Sample Size; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D013777:Tetrazoles; D000077405:Irbesartan