Dapagliflozin Effects on Coronary Calcium and Epicardial Fat Assessed by Cardiotomography

NCT05998525 | Completed Phase 3 DMC

• 1 other identifier: 2
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Calcification of the coronary arteries is a direct sign of atherosclerotic disease of the coronary arteries and has been shown to be a strong predictor of the risk of cardiovascular diseases, including myocardial infarction and/or cardiac death, especially in patients with Diabetes Mellitus type 2. Therefore, there is great interest in pharmacotherapies that improve the rates of cardiovascular complications, and modify the outcomes of this group of patients. Large randomized controlled trials with SGLT2 inhibitors in patients with DM2 have shown a clear reduction in cardiovascular events among individuals with atherosclerotic disease. Atherosclerosis imaging allows measurable assessments of disease progression and activity, revealing early signs of potential drug effects. Noninvasive methods are preferred for serial imaging in drug trials due to the potential risks associated with invasive procedures. The coronary artery calcium quantification using the Agatston score is the most widely used method

Conditions

Diabete Type 2; Unstable Angina; Myocardial Infarction; Diabetes Mellitus, Type 2

Keywords

Dapagliflozin; coronary calcium; Atherosclerosis; Myocardial Infarction; Agatston score

Outcome Measures

Primary Outcomes (2)

• Changes in the coronary calcium score quantified by Agatston's score using simple coronary tomography. Quantified in agatston units (AU)

  Standardized categories have been developed for the calcium score with scores of 0 indicating the absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, 101 to 400 moderate plaque, and \> 400 severe plaque. This is evaluated by the Agatston score. cardiac tomography will be performed on admission prior to hospital discharge and after 12 months of treatment in both groups.

  A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.

• changes in cardiac epicardial fat volume quantified in cm3 and evaluated by simple cardiac tomography.

  Visceral fat depot of the heart and can secrete bioactive molecules that have modulatory effects on the myocardium. Cardiac tomography will be performed on admission prior to hospital discharge and after 12 months of treatment in both groups.

  A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.

Secondary Outcomes (4)

• Number of patients with progression of atherosclerotic disease. The increase in coronary calcium and the increase in epicardial fat after 12 months of treatment will be considered as progression.

  A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.

• Number of patients with new event of acute myocardial infarction

  12 months

• Number of patients with new event of unstable angina

  12 months

• Mortality due to cardiovascular causes

  12 months

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg orally every 24 hours for 12 months

Drug: Dapagliflozin 10Mg Tab

Placebo

PLACEBO COMPARATOR

Placebo orally every 24 hours for 12 months

Drug: Placebo

Interventions

Dapagliflozin 10Mg Tab DRUG

patients who meet the inclusion criteria and after catheterization will be randomized to receive Dapagliflozin 10 mg every 24 hours and upon dischargetreatment will continue for 12 months

Also known as: Forxiga

Dapagliflozin

Placebo DRUG

patients who meet the inclusion criteria and after catheterization will be randomized to receive a placebo pill 24 hours and upon discharge treatment will continue for 12 months

Also known as: Placebo pill

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients over 18 years of age
• Who meet the criteria of the fourth definition of infarction with and without ST segment elevation
• Known with diabetes mellitus 2 or newly diagnosed diabetes according to ADA criteria

You may not qualify if:

• Patients diagnosed with Type 1 Diabetes Mellitus
• Patients on chronic replacement therapy for renal function using peritoneal dialysis or hemodialysis or with GFR less than 30 ml / min / 1.73m2
• Patients who have recently undergone immunosuppressive therapy
• Patients with a history of recurrent urinary tract infection
• Patients known to be allergic to SGLT-2 inhibitors
• Patients presenting as sudden aborted death.
• Patients who after percutaneous coronary intervention require orotracheal intubation or present a state of shock

Sponsors & Collaborators

• Hilda Elizabeth Macías Cervantes: lead

Study Sites (1)

Unidad Medica de Alta Especialidad No. 1, Bajío

León, Guanajuato, 37260,, Mexico

Location

Related Publications (6)

• Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.

  PMID: 31504439 RESULT

• Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell. 2001 Feb 23;104(4):503-16. doi: 10.1016/s0092-8674(01)00238-0. No abstract available.

  PMID: 11239408 RESULT

• Mortensen MB, Dzaye O, Steffensen FH, Botker HE, Jensen JM, Ronnow Sand NP, Kragholm KH, Sorensen HT, Leipsic J, Maeng M, Blaha MJ, Norgaard BL. Impact of Plaque Burden Versus Stenosis on Ischemic Events in Patients With Coronary Atherosclerosis. J Am Coll Cardiol. 2020 Dec 15;76(24):2803-2813. doi: 10.1016/j.jacc.2020.10.021.

  PMID: 33303068 RESULT

• Terasaki M, Hiromura M, Mori Y, Kohashi K, Nagashima M, Kushima H, Watanabe T, Hirano T. Amelioration of Hyperglycemia with a Sodium-Glucose Cotransporter 2 Inhibitor Prevents Macrophage-Driven Atherosclerosis through Macrophage Foam Cell Formation Suppression in Type 1 and Type 2 Diabetic Mice. PLoS One. 2015 Nov 25;10(11):e0143396. doi: 10.1371/journal.pone.0143396. eCollection 2015.

  PMID: 26606676 RESULT

• Hecht HS. Coronary artery calcium scanning: past, present, and future. JACC Cardiovasc Imaging. 2015 May;8(5):579-596. doi: 10.1016/j.jcmg.2015.02.006.

  PMID: 25937196 RESULT

• Macias-Cervantes HE, Martinez-Ramirez DB, Hinojosa-Gutierrez LR, Cordova-Silva DA, Rios-Munoz JA. Effect of dapagliflozin on epicardial fat volume in patients with acute coronary syndrome assessed by computed tomography. Curr Probl Cardiol. 2024 Feb;49(2):102213. doi: 10.1016/j.cpcardiol.2023.102213. Epub 2023 Nov 23.

  PMID: 38000564 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Angina, Unstable; Myocardial Infarction; Atherosclerosis

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The blinding will be double blind, since neither the patient, the responsible investigator, the radiologists and the one who will perform the statistical analysis will know to which group each patient was assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: principal investigator

Model Details: Any patient presenting with a diagnosis of acute myocardial infarction with and without ST segment elevation will be explained the objective of the study and after performing percutaneous coronary intervention they will be randomized using an excel sheet to one of two groups, the intervention group will receive Dapagliflozin 10 mg every 24 hours and the control group will receive placebo. In both groups, a simple cardiotomography was performed to evaluate the calcium score and epicardial fat at baseline and after 12 months of intervention.

Study Record Dates

• First Submitted: June 27, 2021
• First Posted: August 21, 2023
• Study Start: June 21, 2021
• Primary Completion: December 30, 2022
• Study Completion: June 1, 2023
• Last Updated: August 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

ME (1)