RecruitingPhase 3NCT05764057

DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

450 participants

Start Date

Jun 12, 2023

Study Type

INTERVENTIONAL

Conditions

Left Ventricular Dysfunction STEMI AMI NSTEMI

Summary

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

Min Age: 18 Years

Inclusion Criteria6

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;
Ability to provide written informed consent and willing to participate in the 6-month follow-up period.
Affiliation to a national health care system (AME are not allowed).

Exclusion Criteria15

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);
\>1 episode of severe hypoglycemia within the last 6 months under treatment with insulin or sulfonylurea;
Acute symptomatic urinary tract infection (UTI) or genital infection at the time of randomization;
Concomitant treatment (and/or within the 4 weeks prior to the baseline visit) with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozin)
Echocardiographic examination of insufficient quality to permit adequate analysis of the study end-points.
Impossibility to evaluate cardiac remodeling using TTE (e.g., pacemaker or defibrillator …);
Atrial fibrillation rhythm at randomization;
Life expectancy \<6 month;
Known pregnancy at time of randomization;
Breastfeeding women
Females of childbearing potential without adequate contraceptive methods (i.e. sterilization, intrauterine device, vasectomized partner; or medical history of hysterectomy)
Current participation in another interventional trial. Patients under guardianship or curatorship

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Interventions

DRUGDapagliflozin propanediol (FORXIGA™/FARXIGA™1)

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.

DRUGPlacebo comparator

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.