Back to resultsDAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction (DAPAPROTECTOR)
Primary Purpose
AMI, STEMI, NSTEMI
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Dapagliflozin propanediol (FORXIGA™/FARXIGA™1)
Placebo comparator
Sponsored by
About this trial
This is an interventional treatment trial for AMI focused on measuring Acute myocardial infarction, Left ventricular dysfunction, Dapaglioflozin, Transthoracic echocardiography, Cardiac remodeling
Eligibility Criteria
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 ≥30 mL/Min per 1.73m²; Systolic blood pressure (SBP) before first dosing >110 mmHg; Diastolic blood pressure (DBP) before first dosing >70 mmHg; 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: 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); Blood pH <7.32; ; 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
Sites / Locations
- Department of Cardiology AP-HP Hôpital européen Georges - PompidouRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dapagliflozin 10mg daily + standard of care
Placebo + standard of care
Arm Description
Dapagliflozin 10mg per day will be administered orally, as in clinical practice
Placebo will be administered orally
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Change in left ventricular end-systolic volume (LVESV)
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.
Change in left ventricular end-diastolic volume (LVEDV)
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.
Change in LV global longitudinal strain (LS)
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.
Change in left atrial strain (LAS)
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.
Duration of hospital stay (index hospitalization)
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.
All-cause mortality at 6-months
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
Cardiovascular death or worsening HF at 6-months
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
Number of re-admission due to HF at 6-months
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
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
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
Change from baseline to Month 6 (+4 weeks) in plasma levels of NT-pro BNP and HBA1C
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
Change in body weight from baseline to Month 6 (+4 weeks)
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
Adverse events
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.
Full Information
NCT ID
NCT05764057
First Posted
March 1, 2023
Last Updated
September 5, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT05764057
Brief Title
DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction
Acronym
DAPAPROTECTOR
Official Title
DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 12, 2023 (Actual)
Primary Completion Date
June 12, 2025 (Anticipated)
Study Completion Date
December 12, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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 before randomization to confirm inclusion criteria (LVEF≤45%). Four visits are scheduled: at baseline and randomization (Visit D0), at discharge (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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AMI, STEMI, NSTEMI, Left Ventricular Dysfunction
Keywords
Acute myocardial infarction, Left ventricular dysfunction, Dapaglioflozin, Transthoracic echocardiography, Cardiac remodeling
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
450 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dapagliflozin 10mg daily + standard of care
Arm Type
Experimental
Arm Description
Dapagliflozin 10mg per day will be administered orally, as in clinical practice
Arm Title
Placebo + standard of care
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered orally
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin propanediol (FORXIGA™/FARXIGA™1)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo comparator
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (±1 month) by TTE
Description
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
6 months (+4 weeks) from randomization
Title
Change in left atrium volume (LAV) from baseline to Month 6 (±1 month) by TTE
Description
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
6 months (+4 weeks) from randomization
Secondary Outcome Measure Information:
Title
Change in left ventricular end-systolic volume (LVESV)
Description
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.
Time Frame
6 months (+4 weeks) from randomization
Title
Change in left ventricular end-diastolic volume (LVEDV)
Description
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.
Time Frame
6 months (+4 weeks) from randomization
Title
Change in LV global longitudinal strain (LS)
Description
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.
Time Frame
6 months (+4 weeks) from randomization
Title
Change in left atrial strain (LAS)
Description
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.
Time Frame
6 months (+4 weeks) from randomization
Title
Duration of hospital stay (index hospitalization)
Description
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.
Time Frame
6 months (+4 weeks) from randomization
Title
All-cause mortality at 6-months
Description
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
Time Frame
6 months (+4 weeks) from randomization
Title
Cardiovascular death or worsening HF at 6-months
Description
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
Time Frame
6 months (+4 weeks) from randomization
Title
Number of re-admission due to HF at 6-months
Description
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
Time Frame
6 months (±1 month) from randomization
Title
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
Description
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
Time Frame
6 months (+4 weeks) from randomization
Title
Change from baseline to Month 6 (+4 weeks) in plasma levels of NT-pro BNP and HBA1C
Description
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
Time Frame
6 months (+4 weeks) from randomization
Title
Change in body weight from baseline to Month 6 (+4 weeks)
Description
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
Time Frame
6 months (+4 weeks) from randomization
Title
Adverse events
Description
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.
Time Frame
6 months (+4 weeks) from randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 ≥30 mL/Min per 1.73m²;
Systolic blood pressure (SBP) before first dosing >110 mmHg;
Diastolic blood pressure (DBP) before first dosing >70 mmHg;
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:
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);
Blood pH <7.32;
; 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Etienne PUYMIRAT, Pr
Phone
00331.56.09.28.51
Email
etienne.puymirat@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Etienne PUYMIRAT, Pr
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology AP-HP Hôpital européen Georges - Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Etienne PUYMIRAT
Phone
00331.56.09.28.51
Email
etienne.puymirat@aphp.fr
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction
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