Ertugliflozin to Reduce Arrhythmic Burden in ICD/CRT patientS (ERASe-Trial) - a Phase III Study (ERASE)

Ertugliflozin to Reduce Arrhythmic Burden in Implantable Cardioverter-defibrillators (ICD)/Cardiac Resynchronisation Therapy(CRT) patientS (ERASe-Trial) - a Phase III Study

The recent study is planned to investigate the impact of Ertugliflozin on total burden of ventricular arrhythmias. Further objectives will be number of therapeutic interventions of implanted devices, atrial fibrillation, heart failure biomarker and changes in physical function quality of life, stress and anxiety.

Study Overview

• Status: Terminated
• Conditions: Implantable Cardioverter-Defibrillators; Heart Failure With Reduced Ejection Fraction; Cardiac Resynchronization Therapy; Heart Failure With Mid Range Ejection Fraction
• Intervention / Treatment: Drug: Ertugliflozin 5 mg; Drug: Placebo 5mg

Detailed Description

This is a randomized, double-blind (patients and physicians), placebo controlled multi-center study to evaluate the effect of ertugliflozin 5mg once daily (p.o.) for 52 weeks on the ventricular arrhythmic burden and markers of physical and mental well-being as well as biomarker for Heart Failure with reduced Ejection Fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with ICD±CRT therapy. The study will be conducted in 8 experienced sites in Austria with an aim to enrol 402 patients to evaluate the overall study hypothesis.

Therefore, three study visits will be carried out (baseline, 1-year follow-up visit and a telephone visit 4 weeks after visit 2). As part of the two on-site study visits, study-specific measures, a blood sample and an echocardiographic examination will be performed. The trial is completed by a telephone visit 4 weeks after the second on-site visit (week 52).

It is anticipated that the study will run for 30 months.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medical University of Graz
  • Innsbruck, Austria, 620
    • Universitätsklinikum Innsbruck
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Vienna, Austria, 1160
    • Wilhelminenspital
  • Vienna, Austria, 1090
    • Medizinische Universität Wien, AKH Wien
  • Wiener Neustadt, Austria, 2700
    • Landesklinikum Wiener Neustadt
  • Kärnten
    • Klagenfurt, Kärnten, Austria, 9020
      • Klinikum Klagenfurt am Wörthersee
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4021
      • Kepler Universitätsklinikum Linz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. HFrEF or HFmrEF, and ICD±CRT therapy > 3 months

2. at least 10 documented VT episodes (either nsVT (non-sustained ventricular tachycardia) or sVT (sustained ventricular tachycardia) ± ICD (mplantable cardioverter-defibrillator) treatment) within the last 12 months plus:

   • nt-proBNP > 500pg/mL or
   • Left-ventricular Ejection Fraction (LV-EF) < 35% or
   • hospitalization for heart failure within the last 12 months or
   • > 100 nsVTs within the last 12 months
   • > 1 sVT/VF (ventricular function) within the last 12 months
3. Informed consent has to be given in written form.
4. estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73m2
5. Blood pressure before first drug dosing: blood pressure systolic > 100 mmHg
6. Blood pressure before first drug dosing: blood pressure diastolic > 60 mmHg

Exclusion Criteria:

1. Any other form of diabetes mellitus than type 2 diabetes mellitus, history of diabetic ketoacidosis
2. Ongoing ventricular arrhythmia
3. Known allergy to SGLT-2 inhibitors
4. Haemodynamic instability as defined by intravenous administration of catecholamine, calciumsensitizers or phosphodiesterase inhibitors
5. >1 episode of severe hypoglycemia within the last 6 months under treatment with insulin or sulfonylurea
6. Planned catheter ablation for ventricular arrhythmia
7. Planned explantation of ICD, or planned up/downgrade to/from CRT-D device
8. Existing therapy with SGLT-2 inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ertugliflozin; The subject will receive Ertugliflozin 5mg.	Drug: Ertugliflozin 5 mg; The subject will receive Ertugliflozin 5mg orally once daily for 52 weeks.; Other Names: Steglatro
Placebo Comparator: Placebo; The subject will receive Placebo 5mg.	Drug: Placebo 5mg; The subject will receive Placebo 5mg orally daily for 52 weeks.; Other Names: Sugar pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Supraventricular Tachycardia (svT)/ Ventricular Fibrillation (VF) Episodes	Change in number of supraventricular tachycardia (svT)/ ventricular fibrillation (VF) episodes from baseline to week 52	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Nonsustained Ventricular Tachycardia (nsVT) Episodes	Number of nonsustained ventricular tachycardia (nsVT) episodes from baseline to week 52	52 weeks
Number of Episodes of Appropriate Implantable Cardioverter-defibrillator Therapies	Number of episodes of appropriate Implantable cardioverter-defibrillator therapies from baseline to week 52.	52 weeks
Change in NTproBNP Levels	Change in NTproBNP levels from baseline to week 52	52 weeks
Change in HbA1c Levels	Change in HbA1c levels from baseline to week 52	52 weeks
Number of Hospitalizations	Number of hospitalizations from baseline to week 56	56 weeks
Atleast One Hospitalization Due to Heart Failure	It is the number of patients with at least one hospital re-admission due to heart failure from baseline to 56 weeks	56 weeks
Number of Hospitalizations Due to Heart Failure	It is the number of hospital re-admissions due to heart failure from baseline to 56 weeks.	56 weeks
Duration of Hospital Stay	It is the number of days of hospital stay from baseline to 56 weeks	56 weeks
Cardiovascular Mortality	Difference in Cardiovascular mortality between treatment groups from randomisation to week 56	56 weeks

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Medical University of Vienna; Landesklinkum Wiener Neustadt; Klinik Ottakring; Medical University Innsbruck; Klinikum Klagenfurt am Wörthersee; Elisabethinen Hospital; General Hospital Linz
• Investigators: Principal Investigator: Dirk von Lewinski, Assoc-Prof., Medical University of Graz

Publications and helpful links

General Publications

• von Lewinski D, Tripolt NJ, Sourij H, Pferschy PN, Oulhaj A, Alber H, Gwechenberger M, Martinek M, Seidl S, Moertl D, Nurnberg M, Roithinger FX, Steinwender C, Stuhlinger M, Zirlik A, Benedikt M, Kolesnik E, Wallner M, Rohrer U, Manninger M, Scherr D; ERASe study group. Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) - A phase III study. Am Heart J. 2022 Apr;246:152-160. doi: 10.1016/j.ahj.2022.01.008. Epub 2022 Jan 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2021
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Heart failure; ICD; Ertugliflozin; CRT; Sodium dependent glucose transporter-2 inhibitor (SGLT-2); ventricular tachycardia (VT)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Ertugliflozin
• Other Study ID Numbers: DvL-2020-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No