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
- 947 Downloads
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.
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.
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.
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.
KeywordsAtrial fibrillation Atrial Appendage Thrombus Thrombus Resolution Dabigatran NOAC Anticoagulants
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.
- 11.Camm AJ, Lip GY, De Caterina R et al (2012) 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33:2719–2747PubMedCrossRefGoogle Scholar
- 12.Caldeira D, Costa J, Ferreira JJ, Lip GY, Pinto FJ (2015) Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial fibrillation: systematic review and meta-analysis. Clin Res Cardiol Off J German Cardiac Soc. doi: 10.1007/s00392-015-0821-8
- 13.Nielsen PB, Lane DA, Rasmussen LH, Lip GY, Larsen TB (2015) Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol Off J German Cardiac Soc 104:418–429CrossRefGoogle Scholar
- 16.Seidl K, Rameken M, Drogemuller A et al (2002) Embolic events in patients with atrial fibrillation and effective anticoagulation: value of transesophageal echocardiography to guide direct-current cardioversion. Final results of the Ludwigshafen Observational Cardioversion Study. J Am Coll Cardiol 39:1436–1442PubMedCrossRefGoogle Scholar
- 24.Nagamoto Y, Shiomi T, Sadamatsu K (2013) Thrombolytic action of dabigatran in patients with acute pre-existing atrial thrombus. Europace European pacing, arrhythmias, and cardiac electrophysiology. J Working Groups Cardiac Pacing Arrhythmias Cardiac Cell Electrophysiol Eur Soc Cardiol 15:1608Google Scholar
- 28.Dobashi S, Fujino T, Ikeda T (2014) Use of apixaban for an elderly patient with left atrial thrombus. BMJ Case Rep 2014Google Scholar
- 31.Lip GY, Hammerstingl C, Marin F et al (2015) Rationale and design of a study exploring the efficacy of once-daily oral rivaroxaban (X-TRA) on the outcome of left atrial/left atrial appendage thrombus in nonvalvular atrial fibrillation or atrial flutter and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J 169(464–71):e2Google Scholar
- 34.Schulman S, Kearon C (2005) Subcommittee on control of anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. JTH 3:692–694PubMedGoogle Scholar
- 35.Otto C (2002) The practice of clinical echocardiography, 2nd edn. WB Saunders Co, PhiladelphiaGoogle Scholar