DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction

NCT05764057 | Recruiting Phase 3 DMC

• 3 other identifiers: APHP2110542022-001901-28AOM20806
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

AMI; STEMI; NSTEMI; Left Ventricular Dysfunction

Keywords

Acute myocardial infarction; Left ventricular dysfunction; Dapagliflozin; Transthoracic echocardiography; Cardiac remodeling; Cardiovascular Intensive Care Unit (CICU)

Outcome Measures

Primary Outcomes (2)

• 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.

  6 months (+4 weeks) from randomization

• Change in left atrium volume (LAV) 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.

  6 months (+4 weeks) from randomization

Secondary Outcomes (12)

• Change in left ventricular end-systolic volume (LVESV)

  6 months (+4 weeks) from randomization

• Change in left ventricular end-diastolic volume (LVEDV)

  6 months (+4 weeks) from randomization

• Change in LV global longitudinal strain (LS)

  6 months (+4 weeks) from randomization

• Change in left atrial strain (LAS)

  6 months (+4 weeks) from randomization

• Duration of hospital stay (index hospitalization)

  6 months (+4 weeks) from randomization

Study Arms (2)

Dapagliflozin 10mg daily + standard of care

EXPERIMENTAL

Dapagliflozin 10mg per day will be administered orally, as in clinical practice

Drug: Dapagliflozin propanediol (FORXIGA™/FARXIGA™1)

Placebo + standard of care

PLACEBO COMPARATOR

Placebo will be administered orally

Drug: Placebo comparator

Interventions

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.

Dapagliflozin 10mg daily + standard of care

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.

Placebo + standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• AstraZeneca: collaborator

Study Sites (1)

Department of Cardiology AP-HP Hôpital européen Georges - Pompidou

Paris, 75015, France

RECRUITING

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Ventricular Dysfunction, Left

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Ventricular Dysfunction

Study Officials

• Etienne PUYMIRAT, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Etienne PUYMIRAT, Pr

CONTACT

00331.56.09.28.51; etienne.puymirat@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 10, 2023
• Study Start: June 12, 2023
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): October 12, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)