The main objective of this event-driven trial is to demonstrate the superiority of empagliflozin 10 mg once daily versus placebo, in addition to standard of care, for the reduction of the composite endpoint of time to first heart failure…
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
• Composite of time to first HHF or all-cause mortality
Secondary outcome
Key secondary endpoints which are part of the testing strategy:
• Total number of HHF or all-cause mortality
• Total number of non-elective CV hospitalization or all-cause mortality
• Total number of non-elective all-cause hospitalisation or all-cause mortality
• Total number of hospitalisation for MI or all-cause mortality
Other secondary endpoints:
• Time to CV mortality
Background summary
Acute myocardial infarction (MI) affects approximately 7 million individuals
every year. Despite advancements in its treatment, a significant unmet need
persists with more than one third of all MI patients having either died or
developed heart failure (HF) after five years. The observed benefits of
empagliflozin on mortality and hospitalisation for HF (HHF) in patients with
T2D and established atherosclerotic CV disease in the EMPA-REG OUTCOME trial
appeared independent of glucose control and provided a strong rationale to
explore the effects of empagliflozin in populations with established HF.
However, as these benefits were consistent in both patients with and without
HF, a similarly strong rationale exists for exploring efficacy and safety of
empagfliflozin in patients without established but at high risk of developing
HF, frequently represented by patients with an acute MI. Further data with
empagliflozin from animal studies have given additional support by showing
benefits on cardiac remodelling and contractility in the post-acute MI setting.
This trial plans to evaluate efficacy and safety of empagliflozin in patients
with an acute MI, specifically related to effects on the risk of HHF and
mortality. The main hypothesis is that early intervention with empagliflozin vs
placebo on top of standard of care in this patient population reduces the
subsequent risk of HHF and mortality.
Study objective
The main objective of this event-driven trial is to demonstrate the superiority
of empagliflozin 10 mg once daily versus placebo, in addition to standard of
care, for the reduction of the composite endpoint of time to first heart
failure hospitalisation or all-cause mortality in high-risk patients
hospitalised for acute MI.
Study design
A streamlined, randomised, double-blind, parallel group, placebo controlled,
multi-national and multicentre trial
Intervention
Patient will receive medication (IP) in addition to the stnadard treatment -
tablets to be taken daily.
the study visits are at the hospital, though some are online (via app or
computer), for which some questionnaires need to be completed.
Study burden and risks
The main hypothesis is that early intervention with empagliflozin vs placebo on
top of standard of care in this patient population reduces the subsequent risk
of HHF and mortality.
Binger Strasse 173
Ingelheim am Rhein 55216
DE
Binger Strasse 173
Ingelheim am Rhein 55216
DE
Listed location countries
Age
Inclusion criteria
Main Inclusion Criteria:
• Signed and dated written informed consent in accordance with ICH-GCP and
local legislation prior to admission to the trial
• Diagnosis of acute MI (type 1 per the Universal Definition of Myocardial
Infarction [R20-0005]): STEMI or NSTEMI with randomisation to occur no later
than 14 calendar days after hospital admission. For patients with an
in-hospital MI as qualifying event, randomisation must still occur within 14
days of hospital admission.
• High risk of HF, defined as EITHER
a) Symptoms (e.g. dyspnea; decreased exercise tolerance; fatigue), or signs of
congestion (e.g. pulmonary rales,crackles or crepitations; elevated jugular
venous pressure; congestion on chest X-ray), that require treatment (e.g.
augmentation or initiation of oral diuretic therapy; i.v. diuretic therapy;
i.v. vasoactive agent; mechanical intervention etc.) at any time during the
hospitalisation.
OR
b) Newly developed LVEF < 45% as measured by echocardiography,
ventriculography, cardiac CT, MRI or radionuclide imaging during index
hospitalisation.
In addition at least one of the following risk factors:
- Age > 65 years
- Newly developed LVEF < 35%
- Prior MI (before index MI) documented in medical records
- eGFR < 60 ml/min/1.73m2 (according to creatinine from most recent local lab
during the index hospitalisation and calculated with the CKDEPI formula)
- Atrial fibrillation (persistent or permanent ; if paroxysmal, only valid if
associated with index MI)
- Type 2 diabetes mellitus (prior or new diagnosis)
- NTproBNP >1,400 pg/mL for patients in sinus rhythm, >2,800 pg/mL if atrial
fibrillation; BNP >350 pg/mL for patients in sinus rhythm, >700 pg/mL if atrial
fibrillation, measured at any time during hospitalisation
- Uric acid >7.5 mg/dL (>446 µmol/L), measured at any time during
hospitalisation
- Pulmonary Artery Systolic Pressure [or right ventricular systolic pressure]
>40 mmHg (non-invasive [usually obtained from clinically indicated post-MI
echocardiography] or invasive, at any time during hospitalisation)
- Patient not revascularized (and no planned revascularization) for the index
MI (Includes e.g. patients where no angiography is performed, unsuccessful
revascularization attempts, diffuse atherosclerosis not amenable for
intervention; but does NOT include if revascularization was not performed due
to nonobstructive coronary arteries)
- 3-vessel coronary artery disease at time of index MI
- Diagnosis of peripheral artery disease (extracoronary vascular disease, e.g.
lower extremity artery disease or carotid artery disease)
Exclusion criteria
Main Exclusion Criteria:
1) Diagnosis of chronic HF prior to index MI
2) Systolic blood pressure < 90 mmHg at randomisation
3) Cardiogenic shock or use of i.v. inotropes in last 24 hours before
randomisation
4) Coronary Artery Bypass Grafting planned at time of randomisation
5) Current diagnosis of Takotsubo cardiomyopathy
6) Any current severe (stenotic or regurgitant) valvular heart disease
7) eGFR < 20 ml/min/1.73m2 (using CKD-EPI formula based on most recent
creatinine from local lab during hospitalisation) or on dialysis
8) Type I diabetes mellitus
9) History of ketoacidosis
16) Women who are pregnant, nursing, or who plan to become pregnant while in
the trial.
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 | EUCTR2019-001037-13-NL |
| ClinicalTrials.gov | NCT04509674 |
| CCMO | NL75472.042.21 |