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Rationale and design of the RE-LATED AF—AFNET 7 trial: REsolution of Left atrial-Appendage Thrombus—Effects of Dabigatran in patients with Atrial Fibrillation

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Abstract

Background

Dabigatran etexilate, a direct thrombin inhibitor and non-vitamin K antagonist oral anticoagulant (NOAC), has been shown to effectively prevent thromboembolic events in patients with non-valvular atrial fibrillation (AF). However, there is a paucity of data on the antithrombotic efficacy and safety of dabigatran in the resolution of left atrial appendage (LAA) thrombi in AF patients.

Objective

The primary objective of the RE-LATED AF trial is to assess whether dabigatran results in a faster complete LAA thrombus resolution as compared to vitamin K antagonist phenprocoumon. Secondary objectives are to assess the impact of dabigatran on complete LAA thrombus resolution rate within 6 weeks of treatment and change in LAA thrombus volume under treatment. Furthermore, this study aims to assess and compare safety and tolerability of dabigatran vs. phenprocoumon.

Methods

The study is designed as a prospective, randomized, open-label, controlled, explorative, blinded endpoint (PROBE) trial. Patients with AF and left atrial appendage thrombus confirmed by transoesophageal echocardiography (TEE) will be randomized to receive either dabigatran (150 mg bid) or phenprocoumon (INR 2–3) for the resolution of LAA thrombus formation for at least 21 days. Thrombus resolution will be determined by TEE 3 weeks after treatment initiation and subsequently at weeks 4 and 6, if the LAA thrombus has not been resolved before. A total of 110 patients are planned to be randomized.

Conclusion

This is the first prospective, multicentre, randomized controlled clinical trial investigating safety and efficacy of a NOAC for the resolution of LAA thrombi in patients with non-valvular AF.

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Acknowledgments

RE-LATED AF is an investigator-initiated trial (IIT) and supported by a grant of Boehringer Ingelheim Pharma GmbH & Co. KG to and by an additional research grant provided by the University Medical Center of the Johannes Gutenberg-University Mainz. This clinical trial is performed under the patronage of the German Competence Network on Atrial Fibrillation (AFNET e.V.; http://www.kompetenznetz-vorhofflimmern.de/en/home) as RE-LATED AF – AFNET 7 and in close collaboration with AFNET e.V. members and its clinical trial sites. Principal investigator: Thomas Münzel, Mainz. Members of the Steering Committee: Günter Breithardt, Münster (Chairman), Lars Eckardt, Münster, Thomas Rostock, Mainz, Monika Seibert-Grafe, Mainz. Independent Data Monitoring Committee: Dietrich Andresen, Berlin, Wolfgang Köpcke, Münster. Core Laboratories: Andreas Hagendorff, Leipzig, Stephan von Bardeleben, Mainz. We would like to thank all members of these committees as well as all investigators for their contribution to the trial. We would also like to thank members of the BMBF-funded IZKS (Funding No.: 01KN1103) for regulatory work, monitoring, data and safety management.

Conflict of interest

G. Breithardt has previously received educational funds for the AFNET from Boehringer Ingelheim, and he has been on advisory boards of this company. In addition, he has been on advisory boards of Bayer Health Care, Johnson & Johnson, BMS/Pfizer, MSD, Portola, and has received research grants from Meda Pharma, Biosense, St. Jude Medical, Sanofi-Aventis, BMS/Pfizer, and Daiichi-Sankyo, all either provided to the Westfälische Wilhelms-Universität for work done by AFNET or directly to AFNET e.V., Münster, Germany.

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Authors and Affiliations

  1. Interdisciplinary Center for Clinical Trials (IZKS) at the University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany

    Marion Ferner, Daniel Wachtlin, Oliver Deuster & Monika Seibert-Grafe

  2. 2nd Clinic for Internal Medicine at the University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Torsten Konrad, Stephan von Bardeleben, Thomas Münzel & Thomas Rostock

  3. Deutsche Herzstiftung, Frankfurt Am Main, Germany

    Thomas Meinertz

  4. Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany

    Günter Breithardt

  5. Competence Network on Atrial Fibrillation, Münster, Germany

    Günter Breithardt

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  1. Marion Ferner
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  2. Daniel Wachtlin
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Correspondence to Marion Ferner.

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Ferner, M., Wachtlin, D., Konrad, T. et al. Rationale and design of the RE-LATED AF—AFNET 7 trial: REsolution of Left atrial-Appendage Thrombus—Effects of Dabigatran in patients with Atrial Fibrillation. Clin Res Cardiol 105, 29–36 (2016). https://doi.org/10.1007/s00392-015-0883-7

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