About this trial

Recent clinical trials have proven the cardiovascular benefits of new medications for patients with heart failure with reduced ejection fraction (HFrEF), especially sodium-glucose co-transporter 2 (SGLT2) inhibitors. There are no existing randomized clinical trials evaluating the efficacy and safety of dapagliflozin (nor any other SGLT2-inhibitor) to limit cardiac remodeling in patients with acute myocardial infarction (AMI) and left ventricular (LV) dysfunction.

Preventing cardiac remodeling, an established predictor of subsequent heart failure (HF) and cardiovascular death, is likely to translate into benefit in reducing clinical events in post-MI patients.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years;

STEMI (e.g., ST elevation above the J-point of ≥0.1 millivolt in ≥two contiguous leads or left bundle branch block) or very high-risk NSTEMI (e.g., dynamic ECG changes or ongoing chest pain or acute heart failure or hemodynamic instability independent of ECG changes or life-threatening ventricular arrhythmias) with LV dysfunction (LVEF ≤45%); after completion of PCI or angiography procedure

eGFR ≥ 25 mL/Min per 1.73m²;

Systolic blood pressure (SBP) before first dosing >100 mmHg and/or Diastolic blood pressure (DBP) >70 mmHg before first dosing;

Disqualifiers

Cardiogenic shock (SBP <90 mmHg with clinical signs of low output or patients requiring inotropic agents) at randomization;

Referred to surgery for coronary artery bypass grafting (CABG) or treatment of acute complications (e.g. ventricular septal rupture);

Any other form of diabetes than diabetes type 2

History of diabetic ketoacidosis (DKA); Known contra-indication to SGLT-2 inhibitors (hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption);

Trial design

Design model

Parallel

Treatments tested in this trial

Dapagliflozin propanediol (FORXIGA™/FARXIGA™1)
Drug
Dapagliflozin (10 mg per day; per os) on top of standard of care as recommended in current guidelines\* for 6 months (experimental group) \*All patients will receive optimal medical therapy (including antithrombotic, beta-blockers, statins, angiotensin converting enzyme inhibitors or angiotensin receptor blocker or sacubitril/valsartan, diuretics, antagonists of the mineralocorticoid receptor) according to their clinical condition as recommended.
Placebo comparator
Drug
Placebo daily on top of standard of care as recommended in current guidelines\* for 6 months (control group) \*All patients will receive optimal medical therapy (including antithrombotic, beta-blockers, statins, angiotensin converting enzyme inhibitors or angiotensin receptor blocker or sacubitril/valsartan, diuretics, antagonists of the mineralocorticoid receptor) according to their clinical condition as recommended.

Treatment groups

450 Participants

are divided into 2 treatment groups

Group A: Dapagliflozin 10mg daily + standard of careExperimental treatment 1 intervention

Group B: Placebo + standard of carePlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (±1 month) by TTE

Two primary endpoints will allow to evaluate two independent and potent predictors of mortality after AMI: 1) Cardiac systolic function, assessed by change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (+4 weeks) ) by TTE; 2) Remodeling, assessed by change in left atrium volume (LAV) from baseline to Month 6 (+4 weeks) by TTE.

Time frame