Evaluation of the Effect of SGLT-2 Inhibitors on Cardiac Remodeling in Post Myocardial Infarction Patients

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Evaluation of the Effect of Dapagliflozin on Cardiac Remodeling in Post Myocardial Infarction Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05335629
• Other study ID #: Dapagliflozin and ST2
• Status: Completed
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: October 1, 2023

Study information

• Verified date: January 2024
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, randomized, controlled study will be conducted at Clinical Cardioglogy department, Ain Shams University Hospitals, assessing the efficacy and tolerability of SGLT2 inhibitors (dapagliflozin) addition on the clinical outcome and cardiac remodeling markers of post myocardial infarction (MI) diabetic patients

Description:

All patients presenting to the Clinical Cardiology department, Ain Shams University Hospitals, will be assessed for eligibility as follow:

Inclusion criteria:

1. Female or male aged >18 and < 75 years

2. Diabetic post myocardial infarction patients

3. First anterior STEMI with successful TIMI-3 flow

4. STEMI within 12 hrs of onset of chest pain

5. creatine clearance ≥60 mL/min

6. HbA1c between 6.5% and 12.0%

Exclusion criteria:

1. Cardiogenic shock on admission

2. Multivessel disease on admission

3. Mechanical complications e.g. mitral regurge on admission

4. Life threatening arrhythmia on admission

5. Hemodynamic instability on admission

6. Diagnosis of Type 1 diabetes mellitus

7. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time

8. Active urinary infection diagnosed by clinical symptoms of urgency and frequency + lab tests

9. Pregnant or breast-feeding patients

10. Active participation in another clinical study

11. AST or ALT >3x ULN or Total bilirubin >2.5 x ULN

12. CrCl < 60 ml/min (based on the Cockroft-Gault equation)

Eligible patients will be randomly assigned into one of 2 arms:

1. Group 1 (Healthy control) (n=10) Aged-matched healthy volunteers who do not suffer any diseases.

2. Group 2 (Control group) (n= 30): Post-MI patients who will receive standard of care for 4 Weeks

3. Group 3 (Test group) (n= 30): Post-MI patients who will receive standard of care in addition to the SGLT2 Dapagliflozin 10 mg daily for 4 Weeks

• Dapagliflozin will be administered immediately at time of PCI and daily for 4 weeks.

• Standard of care will given to both arms (group 2 and 3) and includes:

Dual Antiplatelet Therapy (DAPT), high intensity statin, anticoagulation therapy, ACEI or aldosterone antagonist depending on the ejection fraction

• All subjects will sign an informed consent statement prior to inclusion in the study.

• All subjects will be followed up for 4 weeks and blood samples will be withdrawn at baseline, 1 week, and the end of the study to test for ST2 (suppression of tumerogenicity 2) biomarker

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Female or male aged >18 and < 75 years

2. Diabetic post myocardial infarction patients

3. First anterior STEMI with successful TIMI-3 flow

4. STEMI within 12 hrs of onset of chest pain

5. creatine clearance =60 mL/min

6. HbA1c between 6.5% and 12.0%

Exclusion Criteria:

1. Cardiogenic shock on admission

2. Multivessel disease on admission

3. Mechanical complications e.g. mitral regurge on admission

4. Life threatening arrhythmia on admission

5. Hemodynamic instability on admission

6. Diagnosis of Type 1 diabetes mellitus

7. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time

8. Active urinary infection diagnosed by clinical symptoms of urgency and frequency + lab tests

9. Pregnant or breast-feeding patients

10. Active participation in another clinical study

11. AST or ALT >3x ULN or Total bilirubin >2.5 x ULN

12. CrCl < 60 ml/min (based on the Cockroft-Gault equation)

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Infarction
• Myocardial Infarction
• Myocardial Remodeling, Ventricular
• Ventricular Remodeling

Intervention

Drug:
• Dapagliflozin 10Mg Tab
Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor (SGLT2 inhibitor) which is a new class of hypoglycemic drugs, and they can block sodium-dependent glucose transporter-2 (SGLT2) located in the early proximal renal tubule to increase urinary glucose excretion and decrease the concentration of blood glucose

Locations

Country	Name	City	State
Egypt	Ain shams university hospitals	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (26)

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Broch K, Andreassen AK, Ueland T, Michelsen AE, Stueflotten W, Aukrust P, Aakhus S, Gullestad L. Soluble ST2 reflects hemodynamic stress in non-ischemic heart failure. Int J Cardiol. 2015 Jan 20;179:378-84. doi: 10.1016/j.ijcard.2014.11.003. Epub 2014 Nov 5. — View Citation

Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020 Sep 21;41(36):3421-3432. doi: 10.1093/eurheartj/ehaa419. — View Citation

Gruzdeva O, Dyleva Y, Uchasova E, Akbasheva O, Karetnikova V, Kashtalap V, Shilov A, Polikutina O, Slepynina Y, Barbarash O. Biological markers and cardiac remodelling following the myocardial infarction. Aging (Albany NY). 2019 Jun 10;11(11):3523-3535. doi: 10.18632/aging.101994. — View Citation

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Lam CSP, Chandramouli C, Ahooja V, Verma S. SGLT-2 Inhibitors in Heart Failure: Current Management, Unmet Needs, and Therapeutic Prospects. J Am Heart Assoc. 2019 Oct 15;8(20):e013389. doi: 10.1161/JAHA.119.013389. Epub 2019 Oct 12. No abstract available. — View Citation

Li C, Zhang J, Xue M, Li X, Han F, Liu X, Xu L, Lu Y, Cheng Y, Li T, Yu X, Sun B, Chen L. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019 Feb 2;18(1):15. doi: 10.1186/s12933-019-0816-2. — View Citation

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Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007 Jun;117(6):1538-49. doi: 10.1172/JCI30634. Epub 2007 May 10. — View Citation

Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Ishikawa K, Watanabe S, Picatoste B, Flores E, Garcia-Ropero A, Sanz J, Hajjar RJ, Fuster V, Badimon JJ. Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics. J Am Coll Cardiol. 2019 Apr 23;73(15):1931-1944. doi: 10.1016/j.jacc.2019.01.056. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect on ST2 (suppression of tumerogenicity 2) level in the acute phase after myocardial infarction	patients will be followed up for the whole period of the study and blood sample will be drawn at baseline and at study end to track changes in the level of ST2 (suppression of tumerogenicity 2) which is a cardiac remodeling biomarker using ELISA technique	4 weeks
Secondary	Echocardiographic changes due to intervention	patients will have their echocardiography and ejection fraction will be compared at baseline and at the end of the study to track any changes that may be caused by intervention	4 weeks