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

Sponsor

Assiut University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05045274

Collaborator

(none)

300

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
STEMI - ST Elevation Myocardial Infarction Left Ventricular Systolic Dysfunction	Drug: Dapagliflozin 10Mg Tab Drug: Placebo	N/A

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

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.
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

Reperfusion therapy: as in study arm
Anti-ischemic treatment: as in study arm.
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:

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:

Primary (main):

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

Secondary (subsidiary):

Echocardiographic parameters at 3 month follow up.
Changes in LV remodeling.
Changes in diastolic function
Changes in LA volume index.
Changes in LV mass index.
Laboratory investigations. Changes of the NT-proBNP from baseline to 3 month follow up
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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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.

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

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.

Outcome Measures

Primary Outcome Measures

Echocardiographic parameter [3 month follow up]
The improvement in the LVEF (≥ 5%) using biplane simpson method echocardiography

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.