Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) – A phase III study

• Published in: The American heart journal 2022-04, Vol.246, p.152-160
• Main Authors: von Lewinski, Dirk, Tripolt, Norbert J, Sourij, Harald, Pferschy, Peter N, Oulhaj, Abderrahim, Alber, Hannes, Gwechenberger, Marianne, Martinek, Martin, Seidl, Sebastian, Moertl, Deddo, Nürnberg, Michael, Roithinger, Franz Xaver, Steinwender, Clemens, Stühlinger, Markus, Zirlik, Andreas, Benedikt, Martin, Kolesnik, Ewald, Wallner, Markus, Rohrer, Ursula, Manninger, Martin, Scherr, Daniel
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood pressure; Body mass index; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Cardiac arrhythmia; Congestive heart failure; Defibrillators, Implantable; Diabetes; Diabetes mellitus; Documentation; Double-Blind Method; Drug dosages; Ejection fraction; Ethics; Fibrillation; Glucose; Health informatics; Heart failure; Heart Failure - drug therapy; Heart Failure - therapy; Humans; Hypotheses; Na+/glucose cotransporter; Oral administration; Patients; Placebos; Stroke Volume - physiology; Tachycardia; Telemedicine; Therapeutic applications; Treatment Outcome; Ventricle; Ventricular Function, Left - physiology
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2022.01.008

Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921