Effect of the Antidiabetic Drug Dapagliflozin on the Coronary Macrovascular and Microvascular Function in Type 2 Diabetic Patients (DAPAMICRO)

April 24, 2024 updated by: Centre Hospitalier Universitaire Saint Pierre

Effect of the Antidiabetic Drug DAPAgliflozin on the Coronary Macrovascular and MICROvascular Function in Type 2 Diabetic Patients

Cardiovascular events remain a major driver of morbidity and mortality in patients with type 2 diabetes mellitus. Diffuse coronary atherosclerosis, combined with impairment of the microcirculation are frequent even in asymptomatic patients and can lead to unfavourable outcomes. In recent years, novel classes of antidiabetic drugs have been introduced, with salutary effects on cardiovascular outcomes of diabetic patients. The sodium-glucose linked transporter 2 (SGLT2) inhibitors - gliflozins - bind to the SGLT2 receptors of the proximal tubule of the nephron and cause glycosuria. They have been shown to have favourable cardiovascular effects by reducing deaths from cardiovascular causes in type 2 diabetic patients.

Moreover, dapagliflozin reduces hospitalisation for heart failure in type 2 diabetic heart failure patients with and without reduced ejection fraction and reduces cardiovascular death and all causes mortality in those with reduced ejection fraction.

It is currently unknown if this is mediated by improvement of coronary physiology both at the level of the epicardial coronary arteries as well as the coronary microcirculation.

The purpose of the study is to explore the impact of dapagliflozin on the coronary and microcirculatory function of type 2 diabetic patients.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 4

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Belgium
    • Bruxelles-Capitale, Région de;Brussels Hoofdstedelijk Gewest
      • Brussels, Bruxelles-Capitale, Région de;Brussels Hoofdstedelijk Gewest, Belgium, 1000
        • CHU Saint Pierre

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • type 2 diabetes mellitus (T2DM) patients presenting with stable angina and a clinical indication for cardiac catheterization
  • T2DM patients with non ST elevation myocardial infarction (NSTEMI) or unstable angina referred for cardiac catheterization
  • Demonstration of coronary lesion(s) with non-significant fractional flow reserve (FFR) values (>0.80), for which revascularisation is deferred
  • Agreement to practice an acceptable method of birth control for women of childbearing potential
  • Signed patient informed consent

Exclusion Criteria:

  • Age < 18 years old
  • T2DM patients presenting with ST elevation myocardial infarction (STEMI)
  • Pregnancy or breastfeeding
  • Body mass index ≥45 kg/m2
  • Creatinine clearance ≤45 ml/min/1.73 m2 (as calculated by Modification of Diet in Renal Disease Study (MDRD ) formula for estimated Glomerular filtration rate (GFR))
  • Indication of liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal during screening or run-in phase
  • Uncontrolled hyperglycemia with glucose >240 mg/dL after an overnight fast
  • Stroke, or transient ischemic attack at presentation and up to 2 months prior to informed consent
  • Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake
  • Any uncontrolled endocrine disorder except type 2 diabetes
  • Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
  • Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body weight
  • Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
  • Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
  • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
  • Planned cardiac surgery or angioplasty within 3 months
  • Any clinical condition that would jeopardize patient safety while participating in this clinical trial
  • Life expectancy < 3 years

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo group
The patient will be treated in standard of care for type 2 diabetic mellitus and will receive a placebo (1 tablet) administered orally daily during 24 weeks
Drug: Placebo
Placebo for dapagliflozin film-coated tablets 10 mg
Experimental: dapagliflozin group
The patient will be treated in standard of care for type 2 diabetic mellitus and will receive Dapagliflozin 10 mg (1 tablet) administered orally daily during 24 weeks
Drug: Dapagliflozin 10 mg Tab
Dapagliflozin 10 mg per day
Other Names:
  • Forxiga®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the longitudinal change of the Fractional Flow Reserve (FRR)
Time Frame: up to 6 months

The longitudinal change (Δ) of FFR is defined as the value at follow-up (6 months) minus the value at baseline.

The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

In the presence of coronary lesions, the degree of percent diameter stenosis will be measured by quantitative coronary angiography and their hemodynamic significance will be evaluated by measuring fractional flow reserve (FFR). According to the guidelines for myocardial revascularisation, only the lesions that have an FFR value equal or less than 0.8 will be treated by coronary angioplasty . In case of angioplasty, FFR will be also measured immediately after successful implantation of the coronary stent.
up to 6 months
the longitudinal change of the Coronary flow reserve (CFR)
Time Frame: up to 6 months

The longitudinal change (Δ) of CFR is defined as the value at follow-up (6 months) minus the value at baseline.

The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

Coronary flow reserve (CFR) will be measured in the vessels of interest, where FFR was measured.
up to 6 months
the longitudinal change of the Index of Microvascular Resistance (IMR).
Time Frame: up to 6 months

The longitudinal change (Δ) of IMR is defined as the value at follow-up (6 months) minus the value at baseline.

The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

The Index of Microvascular Resistance (IMR) will be measured in the vessels of interest, where FFR was measured.
up to 6 months

Collaborators and Investigators

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

Sponsor

Centre Hospitalier Universitaire Saint Pierre

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Panagiotis Xaplanteris, MD, PhD, panagiotis.xaplanteris@stpierre-bru.be

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 6, 2022

Primary Completion (Actual)

July 17, 2023

Study Completion (Actual)

July 17, 2023

Study Registration Dates

First Submitted

May 23, 2022

First Submitted That Met QC Criteria

May 23, 2022

First Posted (Actual)

May 26, 2022

Study Record Updates

Last Update Posted (Estimated)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B0762021210908

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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