Dapagliflozin Effects on Cardiometabolic Outcomes in Patients With an Acute Heart Attack.

Study Overview
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Brief Summary
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This study will evaluate the effect of dapagliflozin versus placebo, given once daily in addition to Standard of Care (SoC) therapies for patients with myocardial infarction (MI), for hospitalisation for heart failure (HHF), cardiovascular (CV) death, and other cardiometabolic outcomes.

Detailed Description
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This is a multicentre, parallel group double-blind, placebo-controlled phase 3 registry-based randomised controlled trial (R-RCT) in patients without diabetes presenting with myocardial infarction (MI) (ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI)) and evidence of impaired regional or global LV systolic function or definite evidence of Q wave MI on ECG. In the study the effect of dapagliflozin versus placebo, given once daily in addition to SoC therapy will be evaluated for the hospitalisation for HF, CV death, and other cardiometabolic outcomes.

Official Title
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A Registry-based, Randomised, Double-blind, Placebo-Controlled Cardiovascular Outcomes Trial to Evaluate the Effect of Dapagliflozin on Cardiometabolic Outcomes in Patients Without Diabetes With Acute Myocardial Infarction at Increased Risk for Subsequent Development of Heart Failure

Conditions
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Acute Myocardial Infarction, Heart Failure

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be ≥18 at the time of signing the informed consent Confirmed MI, either STEMI or NSTEMI, according to the fourth universal definition of MI (Thygesen et al 2019), within the preceding 7 days, or 10 days if earlier randomisation is not feasible Evidence of impaired regional or global LV systolic function at any timepoint during current MI-related hospitalisation (established with echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) or definitive evidence on ECG of Q wave MI (defined as presence of Q waves in two or more contiguous leads, excluding leads III and aVR, and meeting all the following criteria: at least 1.5 mm in depth; at least 30 ms in duration; and, if R wave present, more than 25% of the size of the subsequent R wave) Hemodynamically stable at randomization (no episodes of symptomatic hypotension, or arrhythmia with haemodynamic compromise in the last 24 hours). Male or female Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses Exclusion Criteria: Known type 1 diabetes mellitus (T1DM) or T2DM at the time for admission. Patients with hyperglycaemia, but without a diagnosis of diabetes mellitus prior to the index event, are eligible at the discretion of the Investigator. Patients who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath should be assessed for ketoacidosis, and if ketoacidosis is confirmed the patient should not be randomized. Chronic symptomatic HF with a prior HHF within the last year and known reduced ejection fraction (LVEF≤40 %), documented before the current MI hospitalization Severe (eGFR <20 mL/min/1.73 m2 by local laboratory), unstable or rapidly progressing renal disease at the time of randomization Severe hepatic impairment (Child-Pugh class C) at the time of inclusion into the trial Active malignancy requiring treatment at the time of screening, except for basal cell- or squamous cell carcinoma of the skin, presumed possible to treat successfully Any non-CV condition, eg malignancy, with a life expectancy of less than two years based on the investigator´s clinical judgement Currently on treatment, or with an indication for treatment, with a sodium glucose co-transporter 2 inhibitor (SGLT2-inhibitor)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Patients will be randomized 1:1 to either dapagliflozin or placebo | Drug: Dapagliflozin<br>* Dapagliflozin 10 mg tablets given once daily, per oral use<br>* Other names: Farxiga TM;|
| Placebo Comparator: Placebo<br>Placebo matching dapagliflozin | Drug: Placebo<br>* Placebo matching dapagliflozin 10 mg tablets given once daily, per oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The hierarchical composite endpoint of Death (CV death followed by non-CV death), Hosp due to heart failure (adjudicated followed by investigator reported), Non-fatal MI, AF/flutter event, New onset of T2DM, last visit NYHA class, and weight loss ≥5% |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The hierarchical composite endpoint of Death (CV death followed by non-CV death), Hospitalisation due to heart failure (adjudicated followed by investigator reported), Non-fatal MI, AF/flutter event, New onset of T2DM, and last visit NYHA class |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to the first occurrence of any of the components of this composite: • HHF • CV death |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to the first occurrence of any of the components of this composite: • MI • Stroke (incl. ischaemic, haemorrhagic and undetermined stroke) • CV death |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to CV death |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to the first occurrence of a fatal or a non-fatal MI |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to new onset of T2DM |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Change from baseline in Body weight |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to hospitalisation for any cause |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 
| Time to death of any cause |  | From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Infarction, Cardiovascular Outcome Trial