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

NCT04600921 | Terminated Phase 3 Results DMC

• 1 other identifier: DvL-2020-01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 8

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of Nonsustained Ventricular Tachycardia (nsVT) Episodes

  52 weeks

• Number of Episodes of Appropriate Implantable Cardioverter-defibrillator Therapies

  52 weeks

• Change in NTproBNP Levels

  52 weeks

• Change in HbA1c Levels

  52 weeks

• Number of Hospitalizations

  56 weeks

Study Arms (2)

Ertugliflozin

ACTIVE COMPARATOR

The subject will receive Ertugliflozin 5mg.

Drug: Ertugliflozin 5 mg

Placebo

PLACEBO COMPARATOR

The subject will receive Placebo 5mg.

Drug: Placebo 5mg

Interventions

Ertugliflozin 5 mg DRUG

The subject will receive Ertugliflozin 5mg orally once daily for 52 weeks.

Also known as: Steglatro

Ertugliflozin

Placebo 5mg DRUG

The subject will receive Placebo 5mg orally daily for 52 weeks.

Also known as: Sugar pills

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HFrEF or HFmrEF, and ICD±CRT therapy \> 3 months
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• Klinikum Klagenfurt am Wörthersee: collaborator
• Elisabethinen Hospital: collaborator
• Medical University Innsbruck: collaborator
• Medical University of Vienna: collaborator
• General Hospital Linz: collaborator
• Landesklinkum Wiener Neustadt: collaborator
• Klinik Ottakring: collaborator

Study Sites (8)

Klinikum Klagenfurt am Wörthersee

Klagenfurt, Carinthia, 9020, Austria

Location

Kepler Universitätsklinikum Linz

Linz, Upper Austria, 4021, Austria

Location

Medical University of Graz

Graz, 8010, Austria

Location

Universitätsklinikum Innsbruck

Innsbruck, 620, Austria

Location

Ordensklinikum Linz Elisabethinen

Linz, 4020, Austria

Location

Medizinische Universität Wien, AKH Wien

Vienna, 1090, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

Landesklinikum Wiener Neustadt

Wiener Neustadt, 2700, Austria

Location

Related Publications (2)

• Benedikt M, Oulhaj A, Rohrer U, Manninger M, Tripolt NJ, Pferschy PN, Aziz F, Wallner M, Kolesnik E, Gwechenberger M, Martinek M, Nurnberg M, Roithinger FX, Steinwender C, Widkal J, Leiter S, Zirlik A, Stuhlinger M, Scherr D, Sourij H, von Lewinski D. Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds. NEJM Evid. 2024 Oct;3(10):EVIDoa2400147. doi: 10.1056/EVIDoa2400147. Epub 2024 Sep 1.

  PMID: 39217453 DERIVED

• 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.

  PMID: 35045327 DERIVED

MeSH Terms

Conditions

Heart Failure; Tachycardia, Ventricular

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Tachycardia; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

An important limitation is the lack of generalizability because our study predominantly included White men. A second limitation is that our trial was prematurely stopped, and thus we did not achieve the planned power to accurately assess our primary end point. In addition, seven patients withdrew their consent to continue in the trial. Therefore, the results of our primary and key secondary end points must be interpreted with caution.

Results Point of Contact

• Title: Dr. Dirk von Lewinski
• Organization: Department of Internal Medicine, Division of Cardiology, Medical University of Graz

dirk.von-lewinski@medunigraz.at

+4331638580684

Study Officials

• Dirk von Lewinski, Assoc-Prof.

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 23, 2020
• Study Start: June 24, 2021
• Primary Completion: June 23, 2023
• Study Completion: October 18, 2023
• Last Updated: June 3, 2025
• Results First Posted: June 3, 2025

Record last verified: 2024-11

Locations

AU (8)