E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Heart Failure with preserved Ejection Fraction (HFpEF) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Heart Failure with preserved Ejection Fraction (HFpEF) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076396 |
E.1.2 | Term | Heart failure with preserved ejection fraction |
E.1.2 | System Organ Class | 100000004849 |
|
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 of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test (6MWT) in patients with chronic heart failure (CHF) with preserved ejection fraction (LVEF > 40%). |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess Patient-Reported Outcome (PRO) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Of full age of consent (according to local legislation, usually ≥ 18
years) at screening.
2. Male or female patients. Women of child bearing potential (WOCBP)
must be ready and able to use highly effective methods of birth control
per ICH M3 (R2) that result in a low failure rate of less than 1% per year
when used consistently and correctly. A list of contraception methods
meeting these criteria is provided in the patient information.
3. Signed and dated written informed consent in accordance with
ICHGCP and local legislation prior to admission to the trial
4. Six minute walk test (6MWT) distance ≤350 m at screening and at
baseline.
5. Patients with CHF diagnosed for at least 3 months before Visit 1, and
currently in NYHA class II-IV
6. Chronic heart failure (CHF) with preserved Ejection fraction (EF)
defined as left ventricle ejection fraction(LVEF) > 40 % as per
echocardiography at Visit 1 per local reading and no prior measurement
of LVEF ≤ 40% under stable conditions.
7. Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) > 300
pg/ml for patients without atrial fibrillation (AF), OR > 600 pg/ml for
patients with AF, as analysed at the Central laboratory at Visit 1
8. Patients must have at least one of the following evidence of heart
failure (HF):
a. Structural heart disease (left atrial enlargement and/or left
ventricular hypertrophy) documented by echocardiogram at Visit 1, OR b. Documented Hospitalization for Heart Failure (HHF) within 12 months prior to Visit 1
9. Consistent with prevailing CV guidelines, if oral diuretics are
prescribed to control symptoms, patients must be on an appropriate and
stable dose of oral diuretics for at least 2 weeks prior to Visit 1 to control
symptoms.
10. Clinically stable at randomization with no signs of heart failure
decompensation (as per investigator judgement). |
|
E.4 | Principal exclusion criteria |
1. Myocardial infarction (increase in cardiac enzymes in combination
with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or transient ischemic attack in past 90 days prior to Visit 1
2. Acute decompensated HF (exacerbation of CHF) requiring intravenous
(i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist
device within 4 weeks prior to Visit 1, and/or during screening period
until Visit 2
3. Previous or current randomisation in another Empaglifozin Heart
Failure trial (i.e. studies 1245.110, 1245.121, 1245-0168)
4. Type 1 Diabetes Mellitus (T1DM)
5. Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2
(CKD-EPIcr) or requiring dialysis, as determined at Visit 1
6. Symptomatic hypotension or a systolic blood pressure (SBP) < 100
mmHg at Visit 1 or 2
7. SBP ≥ 180 mmHg at Visit 1 or 2, or SBP >160mmHg at both Visit 1
and 2
8. Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm
documented by ECG at Visit 1 (Screening)
9. Unstable angina pectoris in past 30 days prior to Visit 1
10. Largest distance walked in 6 minutes (6MWTD) at baseline <100m.
11. Any presence of condition that precludes exercise testing such as:
-claudication,
-uncontrolled (according to investigator judgement) bradyarrhythmia or
tachyarrhythmia,
-significant musculoskeletal disease,
-primary pulmonary hypertension,
-severe obesity (body mass index ≥40.0 kg/m2),
-orthopedic conditions that limit the ability to walk (such as arthritis in
the leg, knee or hip injuries)
-amputation with artificial limb without stable prosthesis function for the
past 3 months
-Any condition that in the opinion of the investigator would
contraindicate the assessment of 6MWT
12. Patients in a structured (according to Investigator judgement)
exercise training program in the 1 month prior to screening or planned
to start one during the course of this trial.
13. ICD implantation within 1 month prior to Visit 1 or planned during
the course of the trial
14. Implanted cardiac resynchronisation therapy (CRT)
15. Treatment with i.v. iron therapy or erythropoietin (EPO) within 3
months prior to screening.
16. Further exclusion criteria applies |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. The primary endpoint is the change from baseline to week 12 in
exercise capacity as measured by the distance walked in 6 minutes in
standardised conditions |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline to week 12 in Kansas City Cardiomyopathy
Questionnaire (KCCQ) Total Symptom Score (TSS)
2. Change from baseline to week 12 in Chronic Heart Failure
Questionnaire Self- Administered Standardized format (CHQ-SAS)
dyspnea score
3. Change from baseline to week 6 in exercise capacity as measured by
the distance walked in 6 minutes
4. Change from baseline in Clinical Congestion Score at week 12
5. Change from baseline in Patient Global Impression of Severity (PGI-S)
of Heart Failure Symptoms at week 12
6. Change from baseline in Patient Global Impression of Dyspnea
Severity at week 12
7. Patient Global Impression of Change (PGI-C) in Heart Failure
Symptoms at week 12
8. Patient Global Impression of Change in Dyspnea at week 12
9. Change from baseline in N-terminal pro-brain natriuretic peptide (NT-
proBNP) at week 12 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 0 and Week 12
2. Week 0 and Week 12
3. Week 0 and Week 6
4. Week 0 and Week 12
5. Week 0 and Week 12
6. Week 0 and Week 12
7. Week 12
8. Week 12
9. Week 0 and Week 12 |
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Greece |
Italy |
Poland |
Portugal |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |