Clinical trial NCT04600921: Ertugliflozin to Reduce Arrhythmic Burden in ICD/CRT patientS (ERASe-Trial) - a Phase III Study
Official title: Ertugliflozin to Reduce Arrhythmic Burden in Implantable Cardioverter-defibrillators (ICD)/Cardiac Resynchronisation Therapy(CRT) patientS (ERASe-Trial) - a Phase III Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Heart Failure With Reduced Ejection Fraction
Heart Failure With Mid Range Ejection Fraction
Implantable Cardioverter-Defibrillators
Cardiac Resynchronization Therapy
Keywords: Ertugliflozin
Sodium dependent glucose transporter-2 inhibitor (SGLT-2)
Heart failure
ICD
CRT
ventricular tachycardia (VT)
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Klinikum Klagenfurt am Wörthersee
name: Elisabethinen Hospital
name: Medical University Innsbruck
name: Medical University of Vienna
name: General Hospital Linz
name: Landesklinkum Wiener Neustadt
name: Klinik Ottakring
First posted: 2020-10-23
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Number of Supraventricular Tachycardia (svT)/ Ventricular Fibrillation (VF) Episodes
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of Nonsustained Ventricular Tachycardia (nsVT) Episodes
timeFrame: 52 weeks
measure: Number of Episodes of Appropriate Implantable Cardioverter-defibrillator Therapies
timeFrame: 52 weeks
measure: Change in NTproBNP Levels
timeFrame: 52 weeks
measure: Change in HbA1c Levels
timeFrame: 52 weeks
measure: Number of Hospitalizations
timeFrame: 56 weeks
measure: Atleast One Hospitalization Due to Heart Failure
timeFrame: 56 weeks
measure: Number of Hospitalizations Due to Heart Failure
timeFrame: 56 weeks
measure: Duration of Hospital Stay
timeFrame: 56 weeks
measure: Cardiovascular Mortality
timeFrame: 56 weeks
Other outcomes:
Locations:
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
state: Kärnten
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Linz
state: Oberösterreich
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen
city: Vienna
country: Austria
facility: Medizinische Universität Wien, AKH Wien
city: Vienna
country: Austria
facility: Wilhelminenspital
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
Study officials:
affiliation: Medical University of Graz
name: Dirk von Lewinski, Assoc-Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.