Adolfo Fontenla1, María López-Gil2, Juan Tamargo-Menéndez3, Roberto Matía-Francés4, Ricardo Salgado-Aranda5, Juan Ramón Rey-Blas6, Ángel Miracle-Blanco7, Elena Mejía-Martínez8, Agustín Pastor-Fuentes9, Jorge Toquero-Ramos10, Miguel Ángel Arias11, Isabel Montilla2, Agustín Gómez de la Cámara12, Fernando Arribas2. 1. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: drfontenla@gmail.com. 2. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. 4. Madrid Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain. 5. Servicio de Cardiología, Complejo Hospitalario de Burgos, Burgos, Spain. 6. Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain. 7. Servicio de Cardiología, Hospital Rey Juan Carlos, Móstoles, Madrid, Spain. 8. Servicio de Cardiología, Fundación Jiménez-Díaz, Madrid, Spain. 9. Servicio de Cardiología, Hospital de Getafe, Getafe, Madrid, Spain. 10. Servicio de Cardiología, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. 11. Servicio de Cardiología, Hospital Virgen de la Salud, Toledo, Spain. 12. Unidad de Investigación Clínica en Ensayos Clínicos (UICEC), Hospital 12 de Octubre, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Abstract
INTRODUCTION AND OBJECTIVES:Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT03718273.
RCT Entities:
INTRODUCTION AND OBJECTIVES:Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT03718273.
Authors: Benjamin Hackl; Peter Lukacs; Janine Ebner; Krisztina Pesti; Nicholas Haechl; Mátyás C Földi; Elena Lilliu; Klaus Schicker; Helmut Kubista; Anna Stary-Weinzinger; Karlheinz Hilber; Arpad Mike; Hannes Todt; Xaver Koenig Journal: Front Pharmacol Date: 2022-05-02 Impact factor: 5.988