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

NCT ID: NCT05392959

Last Updated: 2024-04-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-06
• Study Completion Date: 2023-07-17

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for dapagliflozin film-coated tablets 10 mg

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

Group Type: EXPERIMENTAL

Dapagliflozin 10 mg Tab

Intervention Type: DRUG

Dapagliflozin 10 mg per day

Interventions

Dapagliflozin 10 mg Tab

Dapagliflozin 10 mg per day

Intervention Type: DRUG

Placebo

Placebo for dapagliflozin film-coated tablets 10 mg

Intervention Type: DRUG

Other Intervention Names

Forxiga®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Universitaire Saint Pierre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Panagiotis Xaplanteris, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

panagiotis.xaplanteris@stpierre-bru.be

Locations

CHU Saint Pierre

Brussels, Bruxelles-Capitale, Région de;Brussels Hoofdstedelijk Gewest, Belgium

Countries

Belgium

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Other Identifiers

B0762021210908

Identifier Type: -

Identifier Source: org_study_id