The Effect of Early Administration of Dapagliflozin in STEMI Patients With LV Systolic Dysfunction

The Effect of Early Administration of Dapagliflozin in ST Elevation Myocardial Infarction Patients Presenting With Left Ventricular Systolic Dysfunction

300 STIMI patients with LV systolic dysfunction will be divided into two equal groups (Group I (Study arm, n=150); will receive dapagliflozin plus conventional therapy and group (II) Control arm (n=150); will receive conventional therapy only to detect an improvement in the LVEF by ≥ 5

Study Overview

• Status: Not yet recruiting
• Conditions: STEMI - ST Elevation Myocardial Infarction; Left Ventricular Systolic Dysfunction
• Intervention / Treatment: Drug: Dapagliflozin 10Mg Tab; Drug: Placebo

Detailed Description

300 STIMI patients with LV systolic dysfunction will be randomly divided into two equal groups (Group I (Study arm, n=150); will receive

1. Reperfusion therapy: primary percutaneous coronary intervention (PPCI) after DAPT loading (aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally) in the ambulance or emergency department upon diagnosis.
2. Anti-ischemic treatment: DAPT, SC-anticoagulation, beta blockers, statin or others will be individualized according to the patient condition.
3. Anti-failure treatment: Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.
4. Dapagliflozin: It will be given in a dose of 10 mg once daily within 24 hours after PPCI.

Group (II) Control arm (n=150); will receive

1. Reperfusion therapy: as in study arm
2. Anti-ischemic treatment: as in study arm.
3. Anti-failure treatment: as in study arm. LV echocardiographic analysis for both groups at baseline and 3 month follow up by 2D Echocardiography to assess: LVEF by simpson method Diastolic function LV diameter and volume. LA volume index. LV mass index. Severity of MR.

Laboratory investigation substudy analysis:

50 patients from either group will undergo NT-proBNP at baseline and after 3 month follow up.

Clinical outcomes:

Patients will be followed up in a deducted outpatient clinic for assessment of clinical outcomes either by phone cell or clinic visits at 3 month.

Patients will be assessed for the following clinical parameters:

I. Composite of CV death and rehospitalization of HF. II. Individual component at composite end points. III. Reinfarction or readmission for ACS and target lesion revascularization.

Research outcome measures:

a. Primary (main):

1. The improvement in the LVEF (≥ 5%) using biplane simpson method echocardiography.

a. Secondary (subsidiary):

1. Echocardiographic parameters at 3 month follow up.

   1. Changes in LV remodeling.
   2. Changes in diastolic function
   3. Changes in LA volume index.
   4. Changes in LV mass index.
2. Laboratory investigations. Changes of the NT-proBNP from baseline to 3 month follow up
3. Clinical outcomes at 3month. I. Composite of CV death and rehospitalization of HF. II. Individual component at composite end points. III. Reinfarction or readmission for ACS and target lesion revascularization.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1st time STEMI within 24 hours undergoing PPCI. (Chest pain > 30 minutes and ST segment elevation in more than one lead, include the definition of MI with a reference: Third universal definition of MI. (published at ESC Clinical Practice Guidelines 2012).
• LVEF less than 50%.
• eGFR ≥20 mL/min/1.73 m2.

Exclusion Criteria:

• Patients less than 18 years old.
• T1D (Type I diabetes mellitus).
• Hemodynamically unstable.
• Cardiogenic shock (clinical syndrome of tissue hypoperfusion resulting from cardiac dysfunction).
• History of chronic symptomatic HF with a prior hHF within last year
• Patients on dialysis.
• Serious hypersensitivity to dapagliflozin (eg, anaphylaxis, angioedema).
• Pregnant or lactating women.
• Sever hepatic impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: dapagliflozin; (a) Dapagliflozin 10 mg once daily within 24 hours after PPCI for 3 month	Drug: Dapagliflozin 10Mg Tab; Dapagliflozin: It will be given in a dose of 10 mg once daily within 24 hours after PPCI.; Reperfusion therapy: primary percutaneous coronary intervention (PPCI) after DAPT loading (aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally) in the ambulance or emergency department upon diagnosis.; Anti-ischemic treatment: DAPT, SC-anticoagulation, beta blockers, statin or others will be individualized according to the patient condition.; Anti-failure treatment: Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.; Other Names: aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally; DAPT, SC-anticoagulation, beta blockers, statin; Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.
PLACEBO_COMPARATOR: conventional therapy; Reperfusion therapy: primary percutaneous coronary intervention (PPCI) after DAPT loading (aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally) in the ambulance or emergency department upon diagnosis.; Anti-ischemic treatment: DAPT, SC-anticoagulation, beta blockers, statin or others will be individualized according to the patient condition.; Anti-failure treatment: Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.	Drug: Placebo; Reperfusion therapy: primary percutaneous coronary intervention (PPCI) after DAPT loading (aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally) in the ambulance or emergency department upon diagnosis.; Anti-ischemic treatment: DAPT, SC-anticoagulation, beta blockers, statin or others will be individualized according to the patient condition.; Anti-failure treatment: Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.; Other Names: aspirin 300 mg and either clopidogrel 600mg or ticagrelor 180 mg orally; DAPT, SC-anticoagulation, beta blockers, statin; Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineralocorticoid receptor antagonists, other diuretics will be added in case of volume overload.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiographic parameter	The improvement in the LVEF (≥ 5%) using biplane simpson method echocardiography	3 month follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in LV remodeling	using echocardiography	3 month follow up
Changes in diastolic function	using mitral Inflow Patterns electrocardiography	3 month follow up
Changes in LA volume index	using by the biplane area-length method from apical 4- and 2-chamber views electrocardiography	3 month follow up
Changes in LV mass index.	using by linear method electrocardiography	3 month follow up
Laboratory investigations.	Changes of the NT-proBNP from baseline to 3 month follow up	3 month follow up
CV death and rehospitalization of HF	Composite of CV death and rehospitalization of HF	3 month follow up
Individual component at composite end points.	Composite of CV death or rehospitalization of HF	3 month follow up
ACS	Reinfarction or readmission for ACS and target lesion revascularization.	3 month follow up

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (ACTUAL): September 16, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Murmurs; Ventricular Dysfunction; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Systolic Murmurs; Ventricular Dysfunction, Left; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Natriuretic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hormone Antagonists; Serine Proteinase Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Diuretics, Potassium Sparing; Vasoconstrictor Agents; Aspirin; Ticagrelor; Clopidogrel; Dapagliflozin; Diuretics; Enzyme Inhibitors; Mineralocorticoid Receptor Antagonists; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoids; Adrenergic beta-Antagonists; Angiotensin II; Giapreza; Angiotensinogen; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists
• Other Study ID Numbers: GAgban

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No