The main objective of this study is to assess whether in-hospital administration of empagliflozin results in improvement in HF-related outcomes in patients hospitalised for acute heart failure (de novo or decompensated chronic HF) and after initial…
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Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical benefit, a composite of death, number of heart failure events (HFEs)
(including hospitalisations for heart failure (HHFs), urgent heart failure
visits and unplanned outpatient visits), time to first HFE and change from
baseline in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score
(KCCQ-TSS) after 90 days of treatment.
See protocol section 2.1.2
Secondary outcome
* Proportion of patients with a clinically meaningful improvement in KCCQ-TSS
of * 10 points after 90 days of treatment
* Change from baseline in KCCQ TSS after 90 days of treatment
* Change from baseline in log-transformed N-Terminal Pro-Brain * Natriuretic
Peptide (NT-proBNP) level over 30 days of treatment (area under the curve
(AUC)).
* Days alive and out of hospital from study drug initiation until 30 days after
initial hospital discharge
* Days alive and out of hospital from study drug initiation until 90 days after
randomisation
* Time to first occurrence of cardiovascular (CV) death or HFE until end of
trial visit
* Occurrence of HHF until 30 days after initial hospital discharge
* Occurrence of chronic dialysis or renal transplant or sustained reduction of
*40% estimated glomerular filtration rate (eGFR) Chronic Kidney Disease
Epidemiology Collaboration Equation ((CKD-EPI)cr)
* Diuretic effect as assessed by weight loss per mean daily loop diuretic dose
after 15 days of treatment
* Diuretic effect as assessed by weight loss per mean daily loop diuretic dose
after 30 days of treatment
See protocol section 2.1.3
Background summary
Heart failure (HF) is one of the most prevalent chronic diseases associated
with high mortality and morbidity. Over 22 million people around the world
suffer from chronic heart failure (CHF). Patients with HF are at high risk of
mortality and morbidity, 50% die within 5 years of their diagnosis of HF and a
large number are re-hospitalised for exacerbation of HF symptoms. Heart failure
is the most frequent cause of hospital admission among patients 65 years or
older, and there are over 1 million hospitalised patients each year with HF as
a primary diagnosis.
Empagliflozin is an orally available inhibitor of the renal dependent sodium
glucose cotransporter 2 (SGLT-2), promoting urinary glucose excretion.
Empagliflozin is indicated for reduction of blood glucose in patients with Type
2 Diabetes Mellitus (T2DM), and for cardiovascular (CV) death risk reduction in
patients with T2DM and established CV disease.Empagliflozin also reduces blood
pressure, arterial stiffness and measures of myocardial workload, likely
through various mechanisms, as well as improving other CV risk factors (e.g.
uric acid, visceral fat mass, albuminuria.
Other trials with empagliflozin are performed to assess mortality and
morbidity, functional capacity and safety of empagliflozin in patients
with chronic heart failure under stable conditions (i.e. after hospital
discharge). Due to its mode of action (MOA), empagliflozin is expected to
potentially alleviate congestive symptoms seen in patients shortly after
initial stabilisation of acute cardiac decompensation helping to improve heart
failure (HF)-related outcomes within several weeks after discharge from
hospital. In-hospital initiation of different therapies is one of the best
predictors of long-term adherence to medications and long-term improved
prognosis.
See protocol section 1
Study objective
The main objective of this study is to assess whether in-hospital
administration of empagliflozin results in improvement in HF-related outcomes
in patients hospitalised for acute heart failure (de novo or decompensated
chronic HF) and after initial stabilisation.
Secondary objectives are to further assess whether it is safe to start
empagliflozin in patients admitted to hospital in this setting.
See protocol section 2
Study design
Randomised, double-blind, parallel-group, placebo controlled, multinational and
multicentre study.
See protocol section 3.1
Intervention
Patient will receive:
* empagliflozin, dose 10 mg q.d. oral
or
* placebo, q.d. oral
Duration of treatment 90 days
See protocol section 4
Study burden and risks
Empagliflozin is currently indicated for reduction of blood glucose in patients
with T2DM, and for CV death risk reduction in patients with T2DM and
established CV disease.
The safety profile of empagliflozin has been well established in over 15000
patients with T2DM treated in clinical studies (of which more than 10000 were
treated with empagliflozin) with maximum treatment duration of 4 years.
Empagliflozin was tested in over 4600 patients
with T2DM and high CV risk for median treatment duration of 2.6 years
[P15-09840]. In addition, approximately 550 healthy volunteers were exposed to
empagliflozin (up to 800 mg single dose and up to 50 mg multiple dosing). Based
on the mode of action of empagliflozin, which is independent of insulin and
potential concomitant T2DM, it is not expected that the safety profile in
patients without T2DM would be different to that in patients with T2DM.
Because of the mode of action, blockade of the SGLT2 transporter by
empagliflozin leads to glucosuria in patients with and without diabetes,
although with less average daily glucose excretion in non-diabetic patients.
Therefore, it is considered likely that the tolerability of
empagliflozin in non-diabetic patients will be as favourable as in those with
T2DM.
Available data from completed and ongoing trials do not indicate safety
concerns for nondiabetic CHF patients, other than those already described for
patients with T2DM.
See protocol section 1.4
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
1. Currently hospitalised for the primary diagnosis of acute heart failure (de
novo or decompensated chronic HF), regardless of ejection fraction (EF).
Patients with a diagnosis of hospitalized heart failure must have HF symptoms
at the time of hospital admission
2. Evidence of left ventricular ejection fraction (LVEF, either reduced or
preserved EF) as per local reading preferably measured during current
hospitalisation or in the 12 months prior to randomisation
3. Patients must be randomised after at least 24 hours and no later than 5 days
after admission, as early as possible after stabilization and while still in
hospital
4. Patients must fulfil the following stabilisation criteria (while in the
hospital):
- SBP *100mm Hg and no symptoms of hypotension in the preceding 6 hours,
- no increase in i.v. diuretic dose for 6 hours prior to randomisation,
- no i.v. vasodilators including nitrates within the last 6 hours prior to
randomisation
- no i.v. inotropic drugs for 24 hours prior to randomisation.
5. Elevated NT-proBNP * 1600pg/mL or BNP *400 pg/mL according to the local lab,
for patients without atrial fibrillation (AF); or elevated NT-proBNP *
2400pg/mL or BNP *600 pg/mL for patients with AF, measured during the current
hospitalization or in the 72 hours prior to hospital admission,. For patients
treated with an angiotensin receptor neprilysin inhibitor (ARNI) in the
previous 4 weeks prior to randomisation, only NT-proBNP values should be used
6. HF episode leading to hospitalisation must have been treated with a minimum
dose of 40 mg of i.v. furosemide (or equivalent i.v. loop diuretic defined as
20 mg of torasemide or 1 mg of bumetanide)
Exclusion criteria
1. Cardiogenic shock
2. Current hospitalisation for acute heart failure primarily triggered by
pulmonary embolism, cerebrovascular accident, or acute myocardial infarction
(AMI)
3.Current hospitalisation for acute heart failure not caused primarily by
intravascular volume overload;
4. Below interventions in the past 30 days prior to randomisation or planned
during the study:
- Major cardiac surgery, or TAVI (Transcatheter Aortic Valve Implantation), or
PCI, or Mitraclip
- All other surgeries that are considered major according to investigator
judgement
- Implantation of cardiac resynchronisation therapy (CRT) device
- cardiac mechanical support implantation
- Carotid artery disease revascularisation (stent or surgery)
5. Acute coronary syndrome / myocardial infarction, stroke or transient
ischemic attack (TIA) in the past 90 days prior to randomisation
6. Heart transplant recipient, or listed for heart transplant with expectation
to receive a transplant during the course of this trial (according to
investigator judgement), or planned for palliative care for HF, or currently
using left ventricular assist device (LVAD) or intra-aortic balloon pump (IABP)
or any other type of mechanical circulatory support, or patients on mechanical
ventilation, or patients with planned inotropic support in an outpatient setting
7. Haemodynamically significant (severe) uncorrected primary cardiac valvular
disease planned for surgery or intervention during the course of the study
(note: secondary mitral regurgitation or tricuspid regurgitation due to dilated
cardiomyopathy is not excluded unless planned for surgery or intervention
during the course of the study)
8. Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 as measured
during hospitalization (latest local lab measurement before randomisation) or
requiring dialysis
9. Type 1 Diabetes Mellitus (T1DM)
10. History of ketoacidosis, including diabetic ketoacidosis (DKA)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002946-19-NL |
| CCMO | NL72059.042.19 |