Dapagliflozin Effects on Coronary Calcium and Epicardial Fat Assessed by Cardiotomography

August 16, 2023 updated by: Hilda Elizabeth Macías Cervantes

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

It is now well recognized that Coronary Artery Disease (CAD) is part of the spectrum of cardiovascular diseases (CVDs) that have common underlying risk factors and may manifest as myocardial infarction, stroke or death.

CAD is a pathological process characterized by the accumulation of atherosclerotic plaque in the epicardial arteries, whether obstructive or non-obstructive; it can have long and stable periods, but it can also become unstable at any time.

It is unknown whether the high risk provided by the presence of obstructive coronary artery atherosclerotic disease is due to stenosis per se, or due to its correlation with the total burden of atherosclerotic plaque. Studies suggest that calcified atherosclerotic burden, not stenosis, is the main predictor of future events of cardiovascular disease (myocardial infarction and cerebrovascular disease) and death in patients with coronary artery disease.

Atherosclerosis imaging allows measurable assessments of disease progression and activity, revealing early signs of potential drug effects. Non-invasive methods are preferable for serial imaging in drug trials because of the potential risks associated with invasive procedures. High participant dropout rates are also observed when invasive methods are used.

Therefore, coronary artery calcium scanning offers a simple, non-invasive, rapid, and reliable method to quantify coronary calcium, which is pathognomonic for established atherosclerosis. It is a powerful screening tool for asymptomatic patients at low or intermediate risk of CVD, including those with diabetes mellitus, and can potentially improve adherence to lifestyle advice and medication.

Coronary artery calcium can be quantified by non-contrast-enhanced CT using the Agatston score, which is currently the most widely used method. Conceptually, the Agatston score is the sum of the scores for all calcified coronary lesions, representing both the total area and the maximum density of coronary calcification. The area of the lesion is multiplied by the density factor that is determined by pre-defined cut points. The density factor is used so that the regions with higher attenuation contribute more strongly to the final calcium score. A CT attenuation threshold of 130 Hounsfield units (HU) is used for calcium detection, and only contiguous voxels totaling an area greater than 1 mm2 are counted as "lesions" to reduce the influence of image noise. 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.

In 2017, the Society of Cardiovascular Computed Tomography (SCCT) and the Society of Thoracic Radiology (STR) proposed the CAC-DRS as a way to standardize communication regarding CAC findings on non-contrast-enhanced CT scans. CAC-DRS categories are defined as Ax/Ny, where A represents the Agatston score group (where A0, A1, A2, and A3 represent CAC of 0, CAC of 1-99, CAC of 100-299, and CAC ≥ 300, respectively), and N represents the number of vessels affected by CAC, ranging from 0 to 4 for the major epicardial coronary arteries., respectively), and N represents the number of vessels affected by CAC, which varies from 0 to 4 for the main epicardial coronary arteries.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Guanajuato
      • Leon, Guanajuato, Mexico, 37260,
        • Unidad Medica de Alta Especialidad No. 1, Bajío

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dapagliflozin
Dapagliflozin 10 mg orally every 24 hours for 12 months
Drug: Dapagliflozin 10Mg Tab
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
Other Names:
  • Forxiga
Placebo Comparator: Placebo
Placebo orally every 24 hours for 12 months
Drug: Placebo
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
Other Names:
  • Placebo pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the coronary calcium score quantified by Agatston's score using simple coronary tomography. Quantified in agatston units (AU)
Time Frame: A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.
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.
Time Frame: A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: A baseline tomography will be performed at the time of randomization and at 12 months of follow-up.
Determine changes in the total burden of atherosclerotic disease with the use of Dapagliflozin
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
Time Frame: 12 months
Determine the association of the coronary calcium score on the development of acute myocardial infarction in both study groups
12 months
Number of patients with new event of unstable angina
Time Frame: 12 months
Determine the association of the coronary calcium score on the development of unstable angina in both study groups
12 months
Mortality due to cardiovascular causes
Time Frame: 12 months
During the follow-up of the study, the cause of cardiovascular origin will be taken as that related to acute myocardial infarction or worsening of heart failure
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hilda Elizabeth Macías Cervantes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2021

Primary Completion (Actual)

December 30, 2022

Study Completion (Actual)

June 1, 2023

Study Registration Dates

First Submitted

June 27, 2021

First Submitted That Met QC Criteria

August 16, 2023

First Posted (Actual)

August 21, 2023

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2 (Other Identifier: Instituto Cardiovascular de Buenos Aires)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The provision of data can be by direct request to the principal investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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