- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05764057
DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction (DAPAPROTECTOR)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
DAPA-PROTECTOR is a prospective multicenter, randomized, double blind, phase III trial.
Patients with confirmed AMI (e.g., STEMI or very high-risk NSTEMI) with LV dysfunction (LVEF≤45%) after completion of percutaneous coronary intervention (PCI) will be assessed for eligibility. Patients will be randomized (in a 1:1 ratio) to receive dapagliflozin (10mg once day) or placebo for 6 months, on top of standard of care as recommended in current guidelines. Treatment will be prescribed as soon as possible after admission The first TTE (TTE-1) will be performed to confirm inclusion criteria (LVEF≤45%). Four visits are scheduled: at baseline and randomization (Visit D0), at discharge from the CICU (Visit 2) at Month 3 ±2 weeks (Visit 3), and at Month 6 (+ 4 weeks) (Visit 4). After randomization, Visit 2 and Visit 3 will be scheduled to check the tolerance of the drug. In addition, a phone call will be done to the patient to make sure he's not taking any Dapagliflozin (or equivalent as Empagliflozin) in addition to experimental treatment. Finally, the last visit (Visit 4) will be scheduled to collect clinical follow-up and to perform a TTE (TTE-2). Efficacy criteria will be assessed from randomization to Month 6 by TTE. All TTE results will be anonymized and centralized at a Corelab with assessment by independent cardiologists unaware of the patient treatment group.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Etienne PUYMIRAT, Pr
- Phone Number: 00331.56.09.28.51
- Email: etienne.puymirat@aphp.fr
Study Locations
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-
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Paris, France, 75015
- Recruiting
- Department of Cardiology AP-HP Hôpital européen Georges - Pompidou
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Contact:
- Etienne PUYMIRAT
- Phone Number: 00331.56.09.28.51
- Email: etienne.puymirat@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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 Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dapagliflozin 10mg daily + standard of care
Dapagliflozin 10mg per day will be administered orally, as in clinical practice
|
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: Placebo + standard of care
Placebo will be administered orally
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (±1 month) by TTE
Time Frame: 6 months (+4 weeks) from randomization
|
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
Time Frame: 6 months (+4 weeks) from randomization
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of re-admission due to HF at 6-months
Time Frame: 6 months (±1 month) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (±1 month) from randomization
|
Change in left ventricular end-systolic volume (LVESV)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison in each group from baseline to Month 6 (±1 month) using TTE.
To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction.
|
6 months (+4 weeks) from randomization
|
Change in left ventricular end-diastolic volume (LVEDV)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison in each group from baseline to Month 6 (+4 weeks) using TTE.
To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction.
|
6 months (+4 weeks) from randomization
|
Change in LV global longitudinal strain (LS)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison in each group from baseline to Month 6 (+4 weeks) using TTE.
To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction.
|
6 months (+4 weeks) from randomization
|
Change in left atrial strain (LAS)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison in each group from baseline to Month 6 (+4 weeks) using TTE.
To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction.
|
6 months (+4 weeks) from randomization
|
Duration of hospital stay (index hospitalization)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction.
|
6 months (+4 weeks) from randomization
|
All-cause mortality at 6-months
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (+4 weeks) from randomization
|
Cardiovascular death or worsening HF at 6-months
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (+4 weeks) from randomization
|
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
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (+4 weeks) from randomization
|
Change from baseline to Month 6 (+4 weeks) in plasma levels of NT-pro BNP and HBA1C
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (+4 weeks) from randomization
|
Change in body weight from baseline to Month 6 (+4 weeks)
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction
|
6 months (+4 weeks) from randomization
|
Adverse events
Time Frame: 6 months (+4 weeks) from randomization
|
Comparison between both groups (experimental vs. placebo) of 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]. To assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction. |
6 months (+4 weeks) from randomization
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Etienne PUYMIRAT, Pr, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- Ventricular Dysfunction
- Ventricular Dysfunction, Left
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Sodium-Glucose Transporter 2 Inhibitors
- Dapagliflozin
Other Study ID Numbers
- APHP211054
- 2022-001901-28 (EudraCT Number)
- AOM20806 (Other Grant/Funding Number: Other Grant/Funding Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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