title: 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).
abstract: There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban (Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and natural history of LA/LAA thrombi. Unique data on clot resolution with rivaroxaban in a prospective cohort would be obtained in X-TRA.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom. Electronic address: g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Medicine II, Heart Center Bonn, University Hospital, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hammerstingl
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Marin
authors.affiliation: Arrhythmia and Electrophysiology Center, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cappato
authors.affiliation: Global Medical Affairs, Bayer HealthCare, Berlin, Germany.
authors.forename: Isabelle Ling
authors.initials: IL
authors.lastname: Meng
authors.affiliation: Global Research and Development Statistics, Bayer HealthCare, Berlin, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Kirsch
authors.affiliation: Therapeutic Cardiovascular and Coagulation, Global Development, Bayer HealthCare, São Paulo, Brazil.
authors.forename: Eolo
authors.initials: E
authors.lastname: Morandi
authors.affiliation: Global Medical Affairs, Bayer HealthCare, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: van Eickels
authors.affiliation: Cardiology Department, Assistance Publique-Hôpitaux de Paris and Université Pierre-et-Marie-Curie, Saint-Antoine University and Medical School, Paris, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000284:Administration, Oral; D020517:Atrial Appendage; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D017115:Catheter Ablation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017548:Echocardiography, Transesophageal; D004554:Electric Countershock; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D009025:Morpholines / Q000008:administration & dosage; D012189:Retrospective Studies; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome; D016032:Randomized Controlled Trials as Topic; D015337:Multicenter Studies as Topic; D064887:Observational Studies as Topic
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D000069552:Rivaroxaban; D013876:Thiophenes