Clinical Drug Investigation

, Volume 28, Issue 9, pp 565–572

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
  • Andreas Goette
  • Alessandra D’Alessandro
  • Alicja Bukowska
  • Siegfried Kropf
  • Christian Mewis
  • Christoph Stellbrink
  • Jürgen Tebbenjohanns
  • Christian Weiss
  • Uwe Lendeckel
Original Research Article

DOI: 10.2165/00044011-200828090-00003

Cite this article as:
Goette, A., D’Alessandro, A., Bukowska, A. et al. Clin. Drug Investig. (2008) 28: 565. doi:10.2165/00044011-200828090-00003

Abstract

Background and 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-β1, tumour necrosis factor-α, interleukin-6) and oxidative stress parameters (8-iso-prostaglandin F) will be determined after each treatment phase and compared with baseline levels.

Conclusion: 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.

ClinicalTrials.gov identifier: NCT00613496.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Andreas Goette
    • 1
  • Alessandra D’Alessandro
    • 1
  • Alicja Bukowska
    • 2
  • Siegfried Kropf
    • 3
  • Christian Mewis
    • 4
  • Christoph Stellbrink
    • 5
  • Jürgen Tebbenjohanns
    • 6
  • Christian Weiss
    • 7
  • Uwe Lendeckel
    • 2
  1. 1.Department of CardiologyOtto-von-Guericke-University HospitalMagdeburgGermany
  2. 2.Institute for Experimental Internal MedicineOtto-von-Guericke-University HospitalMagdeburgGermany
  3. 3.Institute for Biometry and Medical InformaticsOtto-von-Guericke-University HospitalMagdeburgGermany
  4. 4.Hospital for Internal Medicine IIIUniversity of SaarlandHomburgGermany
  5. 5.Städtische Kliniken BielefeldBielefeldGermany
  6. 6.STK HildesheimWeinberg, HildesheimGermany
  7. 7.II. Medical Hospital and AmbulanceJohannes Gutenberg-University MainzMainzGermany

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