dapagliflozin for Acute myocardial infarction | Heart failure

Inclusion criteria

• {"criterion_text":"- Age ≥18 years"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- eGFR ≥25 mL/Min per 1.73m²"}
• {"criterion_text":"- Systolic blood pressure (SBP) before first dosing >100 mmHg and/or Diastolic blood pressure (DBP) >70 mmHg before first dosing"}
• {"criterion_text":"- Ability to provide written informed consent and willing to participate in the 6-month follow-up period."}
• {"criterion_text":"- Affiliation to a national health care system (AME are not allowed)."}

Exclusion criteria

• {"criterion_text":"- Cardiogenic shock (SBP <90 mmHg with clinical signs of low output or patients requiring inotropic agents) at randomization"}
• {"criterion_text":"- Referred to surgery for coronary artery bypass grafting (CABG) or treatment of acute complications (e.g. ventricular septal rupture)"}
• {"criterion_text":"- Any other form of diabetes than diabetes type 2"}
• {"criterion_text":"- History of diabetic ketoacidosis (DKA)"}
• {"criterion_text":"- Known contra-indication to SGLT-2 inhibitors (hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption)"}
• {"criterion_text":"- >1 episode of severe hypoglycemia within the last 6 months under treatment with insulin or sulfonylurea"}
• {"criterion_text":"- Acute symptomatic urinary tract infection (UTI) or genital infection at the time of randomization"}
• {"criterion_text":"- Concomitant long-term treatment (and/or within the 4 weeks prior to the baseline visit) with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozine)"}
• {"criterion_text":"- Echocardiographic examination of insufficient quality to permit adequate analysis of the study end-points."}
• {"criterion_text":"- Patients with a known hypersensitivity to dapagliflozine or any of the excipients of the product."}
• {"criterion_text":"- Impossibility to evaluate cardiac remodeling using TTE (e.g., pacemaker or defibrillator …)"}
• {"criterion_text":"- Atrial fibrillation rhythm at randomization"}
• {"criterion_text":"- Life expectancy <6 month"}
• {"criterion_text":"- Known pregnancy at time of randomization"}
• {"criterion_text":"- Breastfeeding women"}
• {"criterion_text":"- Females of childbearing potential without adequate contraceptive methods (i.e. sterilization, intrauterine device, vasectomized partner; or medical history of hysterectomy)"}
• {"criterion_text":"- Current participation in another interventional trial"}
• {"criterion_text":"- Patients under guardianship or curatorship"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (+4 weeks) measured by transthoracic echocardiography (TTE)."}
• {"endpoint_text":"- 2) Remodeling, assessed by change in left atrium volume (LAV) from baseline to Month 6 ) (+4 weeks) by TTE","definition_or_measurement_approach":"Change in left atrium volume (LAV) from baseline to Month 6 (+4 weeks) measured by transthoracic echocardiography (TTE)."}

Secondary endpoints

• {"endpoint_text":"- Secondary endpoints: comparison in each group from baseline to Month 6 (+ 4 weeks) using TTE - Change in left ventricular end-systolic volume (LVESV) - Change in left ventricular end-diastolic volume (LVEDV) - Change in LV global longitudinal strain (LS) - Change in left atrial strain (LAS)","definition_or_measurement_approach":"Changes in LVESV, LVEDV, LV global longitudinal strain and left atrial strain from baseline to Month 6 (+4 weeks) measured by TTE."}
• {"endpoint_text":"- Secondary endpoints: comparison between both groups (experimental vs. placebo) - Duration of hospital stay (index hospitalization) - All-cause mortality at 6-months - Cardiovascular death or worsening HF at 6-months - Number of re-admission due to HF at 6-months","definition_or_measurement_approach":"Between-group comparisons (experimental vs placebo) for clinical outcomes measured up to 6 months, including hospital stay duration, all-cause mortality, cardiovascular death or worsening heart failure, and HF re-admissions at 6 months."}
• {"endpoint_text":"- Change from baseline to Month 6 (+ 4 weeks) in LVESV, LVEDV, LAV, LVEF, LV global LS, LAS and pulmonary congestion (normal lung, mild, moderate or severe ultrasound lung comets [ULCs]) using TTE at month 6 - Change from baseline to Month 6 (+ 4 weeks) in plasma levels of NT-pro BNP and HBA1C - Change in body weight from baseline to Month 6 (+4 weeks)","definition_or_measurement_approach":"Echocardiographic measures (LVESV, LVEDV, LAV, LVEF, LV global LS, LAS, pulmonary congestion via ULCs) at month 6 by TTE; plasma NT-proBNP and HbA1c measured from baseline to Month 6; change in body weight from baseline to Month 6."}
• {"endpoint_text":"- Adverse events, with particular focus to those potentially related to dapagliflozin complications (e.g., all symptoms of volume depletion, major hypoglycemia, genital infections, diabetes ketoacidosis, changes in liver function parameters [ASAT, ALAT ≥3 USN], changes in renal function parameters [creatine x2, eGFR <30 mL/Min per 1.73m²]), fractures, and lower limb amputations) at Month 6)","definition_or_measurement_approach":"Safety monitoring of adverse events up to Month 6 with special focus on events potentially related to dapagliflozin (volume depletion, major hypoglycemia, genital infections, DKA, liver and renal parameter changes, fractures, amputations) using clinical assessments and laboratory measurements."}

France

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

360

Number Of Sites

32

Number Of Participants

450

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France