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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Heart Failure With Reduced Ejection Fraction, Heart Failure With Mid Range Ejection Fraction, Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy

Intervention / Treatment
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* Drug: Ertugliflozin 5 mg
* Drug: Placebo 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HFrEF or HFmrEF, and ICD±CRT therapy > 3 months 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 Informed consent has to be given in written form. estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73m2 Blood pressure before first drug dosing: blood pressure systolic > 100 mmHg Blood pressure before first drug dosing: blood pressure diastolic > 60 mmHg Exclusion Criteria: Any other form of diabetes mellitus than type 2 diabetes mellitus, history of diabetic ketoacidosis Ongoing ventricular arrhythmia Known allergy to SGLT-2 inhibitors Haemodynamic instability as defined by intravenous administration of catecholamine, calciumsensitizers or phosphodiesterase inhibitors >1 episode of severe hypoglycemia within the last 6 months under treatment with insulin or sulfonylurea Planned catheter ablation for ventricular arrhythmia Planned explantation of ICD, or planned up/downgrade to/from CRT-D device Existing therapy with SGLT-2 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ertugliflozin<br>The subject will receive Ertugliflozin 5mg. | Drug: Ertugliflozin 5 mg<br>* The subject will receive Ertugliflozin 5mg orally once daily for 52 weeks.<br>* Other names: Steglatro;|
| Placebo Comparator: Placebo<br>The subject will receive Placebo 5mg. | Drug: Placebo 5mg<br>* The subject will receive Placebo 5mg orally daily for 52 weeks.<br>* Other names: Sugar pills;|

What is the study measuring?
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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 appropriate therapeutic ICD therapies | Number of appropriate therapeutic ICD therapies from baseline to week 52 | 52 weeks | 
| Change in nt-proBNP levels | Change in nt-proBNP levels from baseline to week 52 | 52 weeks | 
| Change of HbA1c | Change of HbA1c from baseline to week 52 | 52 weeks | 
| Number of hospital re-admissions due to heart failure | Number of hospital re-admissions due to heart failure from baseline to week 56 | 56 weeks | 
| Duration of hospital stay | Duration of hospital stay from baseline to week 56 | 56 weeks | 
| Cardiovascular Mortality | Cardiovascular Mortality from baseline to week 56 | 56 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ertugliflozin, Sodium dependent glucose transporter-2 inhibitor (SGLT-2), Heart failure, ICD, CRT, ventricular tachycardia (VT)