Acute Myocardial Infarction, Heart failure
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be =18 at the time of signing the informed consent. 2 Confirmed MI, either STEMI or NSTEMI, according to the fourth universal definition of MI (Thygesen et al 2019), within the preceding 7 days, or 10 days if earlier randomisation is not feasible. 3. Evidence of impaired regional or global LV systolic function at any timepoint during current MI-related hospitalisation (established with echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) OR definitive evidence on ECG of Q wave MI (defined as presence of Q waves in 2 or more contiguous leads, excluding leads III and aVR, and meeting all the following criteria: at least 1.5mm in depth; at least 30 ms in duration; and, if R wave present, more than 25% of the size of the subsequent R wave). 4. Haemodynamically stable at randomisation (no episodes of symptomatic hypotension, or arrhythmia with haemodynamic compromise in the last 24 hours). 5. Male or female 6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol 7. Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1750
Exclusion criteria
Exclusion criteria: 1. Known T1DM or T2DM at the time for admission. Patients with hyperglycaemia, but without a diagnosis of diabetes mellitus prior to the index event, are eligible at the discretion of the Investigator. Patients who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath should be assessed for ketoacidosis, and if ketoacidosis is confirmed the patient should not be randomized. 2. Chronic symptomatic HF with a prior HHF within the last year and known reduced ejection fraction (LVEF=40 %), documented before the current MI hospitalization. 3. Severe (eGFR <20 mL/min/1.73 m2 by local laboratory), unstable or rapidly progressing renal disease at the time of randomization. 4. Severe hepatic impairment (Child-Pugh class C) at the time of inclusion into the trial. 5. Active malignancy requiring treatment at the time of screening, except for basal cell- or squamous cell carcinoma of the skin, presumed possible to treat successfully. 6. Any non-CV condition, eg malignancy, with a life expectancy of less than two years based on the investigator´s clinical judgement. 7. Currently on treatment, or with an indication for treatment, with a SGLT2-inhibitor. 8. Known intolerance to dapagliflozin 9. Participation in another study with a non-approved investigational drug or blinded treatment with a CV or glucose lowering medication. 10. Involvement in the planning and/or conduct of the study (applies to AZ staff, UCR staff and/or staff at the study site). 11. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements, or any condition in the opinion of the Investigator that would make participation unsafe or unsuitable. 12. Previous randomisation in the present study. 13. Women of childbearing potential (ie, those who are not chemically or surgically sterilised or postmenopausal): (a) Who are not willing to use a highly effective method of contraception (described below), OR (b) Who have a positive pregnancy test, OR (c) Who are breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the clinical benefit of dapagliflozin 10 mg once daily (QD) is superior in relation to placebo when added to SoC in patients without diabetes with myocardial infarction and impaired left ventricular systolic function during the index MI hospitalisation. Clinical benefit is reduced risk of Death, Heart Failure, non-fatal MI, AF/flutter, new onset of T2DM, symptoms of HF as measured by NYHA class, as well as reduced Body weight, in relation to placebo;Secondary Objective: -To determine whether the clinical benefit of dapagliflozin 10 mg once daily (QD) is superior in relation to placebo when added to SoC. Clinical benefit is reduced risk of Death, Heart Failure, non-fatal MI, AF/flutter, new onset of T2DM and symptoms of HF as measured by NYHA class, in relation to placebo -To demonstrate the superiority of dapagliflozin 10 mg once daily (QD) versus dapagliflozin 10 mg placebo to match in reducing the incidence of CV death or HHF when added to SoC -To determine whether dapagliflozin 10 mg QD is superior to placebo in reducing: - MI, stroke or CV death (MACE) when added to SoC - the incidence of CV death when added to SoC - the incidence of fatal or non-fatal MI when added to SoC - the incidence of new onset T2DM in MI patients when added to SoC - Body Weight when added to SoC - the incidence of hospitalisation for any cause when added to SoC - the incidence of all-cause mortality when added to SoC;Primary end point(s): The hierarchical composite endpoint of: 1. Death (first CV death, followed by non-CV death) 2. Hospitalisation due to heart failure (first adjudicated, followed by investigator reported) 3. Non-fatal MI 4. AF/flutter event 5. New onset of T2DM 6. NYHA class at last visit 7. Body weight decrease of at least 5% at last visit;Timepoint(s) of evaluation of this end point: Last Subject Last Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The hierarchical composite endpoint of: 1. Death (first CV death, followed by non-CV death) 2. Hospitalisation due to heart failure (first adjudicated, followed by investigator reported) 3. Non-fatal MI 4. AF/flutter event 5. New onset of T2DM 6. NYHA class at last visit -Time to the first occurrence of any of the components of this composite: • HHF • CV death -Time to the first occurrence of any of the components of this composite: • MI • Stroke (incl. ischaemic, haemorrhagic and undetermined stroke) • CV death -Time to CV death -Time to the first occurrence of a fatal or a non-fatal MI -Time to new onset of T2DM -Change from baseline in Body weight -Time to hospitalisation for any cause -Time to death of any cause;Timepoint(s) of evaluation of this end point: Last Subject Last Visit | — |
Countries
Sweden, United Kingdom
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed