E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart failure |
Herzinsuffizienz |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure |
Herzinsuffizienz |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate the impact of ertugliflozin on ventricular arrhythmia burden. |
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E.2.2 | Secondary objectives of the trial |
Further objectives will be the number of therapeutic interventions of implanted devices, atrial fibrillation, heart failure biomarker and changes in physical function. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) HFrEF or HFmrEF and ICD±CRT therapy > 3 months 2) Least 10 documented VT episodes (either nsVT or sVT ± ICD treatment) within the last 12 months plus - nt-proBNP > 500pg/mL or - LV-EF < 35% or - hospitalization for heart failure within the last 12 months or - >100nsVTs within the last 12 months- > 1 sVT/VF within the last 12 months 3) Informed consent has to be given in written form. 4) eGFR > 30 ml/min/1.73m2 5) Blood pressure before first drug dosing: RRsystolic >100mmHg 6) Blood pressure before first drug dosing: RRdiastolic >60mmHg 7) 18 – 80 years of age
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E.4 | Principal 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) Hemodynamic instability as defined by intravenous administration of catecholamine, calcium-sensitizers 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 within upcoming 12 months 7) Planned explantation of ICD, or planned up/downgrade to/from CRT-D device within upcoming 12 months 8) Existing therapy with SGLT-2 inhibitors
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in number of sVT/VF episodes between treatment groups from randomization to week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Difference in nsVT episodes between treatment groups from randomization to week 52 Difference in number of appropriate therapeutic ICD therapies between groups from randomization to week 52 Difference in the change of nt-proBNP levels between treatment groups from randomization to week 52 Difference in the change of HbA1c between treatment groups from randomization to week 52 (in subjects with known T2DM) Difference in the number of hospital re-admissions due to heart failure between the treatment groups Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment Difference in cardiovascular mortality between treatment groups from randomization to week 52
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | 0 |