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

Phase 3

Terminated

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

• Registration Number: NCT04600921
• Lead Sponsor: Medical University of Graz

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-10-19
• Study First Submitted QC: 2020-10-19
• Study First Posted: 2020-10-23
• Study Start: 2021-06-24
• Primary Completion: 2023-06-23
• Status Verified: 2023-10
• Study Completion: 2023-10-18
• Last Update Submitted: 2023-10-18
• Last Update Posted: 2023-10-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

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

2. at least 10 documented VT episodes (either nsVT or sVT ± ICD 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 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo 5mg	The subject will receive Placebo 5mg.
Ertugliflozin	Ertugliflozin 5 mg	The subject will receive Ertugliflozin 5mg.

Primary Outcome Measures

Name	Time	Method
Change in number of supraventricular tachycardia (svT)/ ventricular fibrillation (VF) episodes	52 weeks	Change in number of supraventricular tachycardia (svT)/ ventricular fibrillation (VF) episodes from baseline to week 52

Secondary Outcome Measures

Name	Time	Method
Number of hospital re-admissions due to heart failure	56 weeks	Number of hospital re-admissions due to heart failure from baseline to week 56
Number of appropriate therapeutic ICD therapies	52 weeks	Number of appropriate therapeutic ICD therapies from baseline to week 52
Change of HbA1c	52 weeks	Change of HbA1c from baseline to week 52
Number of nonsustained ventricular tachycardia (nsVT) episodes	52 weeks	Number of nonsustained ventricular tachycardia (nsVT) episodes from baseline to week 52
Change in nt-proBNP levels	52 weeks	Change in nt-proBNP levels from baseline to week 52
Duration of hospital stay	56 weeks	Duration of hospital stay from baseline to week 56
Cardiovascular Mortality	56 weeks	Cardiovascular Mortality from baseline to week 56

Trial Locations

Locations (8)

Wilhelminenspital; 🇦🇹 Vienna, Austria

Kepler Universitätsklinikum Linz; 🇦🇹 Linz, Oberösterreich, Austria

Landesklinikum Wiener Neustadt; 🇦🇹 Wiener Neustadt, Austria

Medizinische Universität Wien, AKH Wien; 🇦🇹 Vienna, Austria

Klinikum Klagenfurt am Wörthersee; 🇦🇹 Klagenfurt, Kärnten, Austria

Medical University of Graz; 🇦🇹 Graz, Austria

Ordensklinikum Linz Elisabethinen; 🇦🇹 Linz, Austria

Universitätsklinikum Innsbruck; 🇦🇹 Innsbruck, Austria