DAPAGLIFLOZIN for Coronary artery disease|Prediabetes|Coronary atherosclerosis|Coronary heart disease

Inclusion criteria

• {"criterion_text":"- Age 18-80"}
• {"criterion_text":"- Diagnosed coronary artery disease (coronary artery stenosis of at least 20% with a reference diameter of >2.5 mm detected in a coronary CT scan or after percutaneous coronary revascularization)"}
• {"criterion_text":"- Core CT scan performed <3 months after inclusion in the study, of at least good quality"}
• {"criterion_text":"- Prediabetes defined as fasting blood glucose 100-125 mg% or Hba1c 5.70 6.49% (measurement documented during the screening/randomization visit or within 30 days before the screening/randomization visit) or a documented positive result of the oral stress test glucose (fasting blood glucose 100-125 mg% and 140-199 mg% 2 hours after an oral load of 75 g of glucose) performed within 30 days before the screening/randomization visit"}
• {"criterion_text":"- Stable treatment and control of cardiovascular risk factors, including dietary and lifestyle management, for at least 4 weeks."}
• {"criterion_text":"- Willingness and ability to provide informed consent for participation in the study."}
• {"criterion_text":"- Capability and willingness, in the opinion of the investigator, to comply with all study requirements"}

Exclusion criteria

• {"criterion_text":"- Severe valvular disease"}
• {"criterion_text":"- Severe diseases of the musculoskeletal system requiring specific rehabilitation recommendations"}
• {"criterion_text":"- Decompensated heart failure"}
• {"criterion_text":"- Lack of consent to participate in the study"}
• {"criterion_text":"- Severe arrhythmia/unexplained loss of consciousness"}
• {"criterion_text":"- Other contraindications to physical exercise"}
• {"criterion_text":"- Presence of an artificial valve, cardiac pacing system or other implantable device (e.g. cardioverter-defibrillator)"}
• {"criterion_text":"- Use of glucose-lowering medications other than metformin"}
• {"criterion_text":"- Use of weight loss medications"}
• {"criterion_text":"- Condition after bariatric surgery"}
• {"criterion_text":"- Diagnosed liver disease or ALT, AST greater than three times the upper limit of normal at the screening visit"}
• {"criterion_text":"- History of pancreatitis or active pancreatitis"}
• {"criterion_text":"- Decompensated hyperthyroidism"}
• {"criterion_text":"- History of anaphylactic shock after administration of iodine contrast"}
• {"criterion_text":"- Chronic kidney disease (GFR <60 ml/min/1.73 m2)"}
• {"criterion_text":"- Participation in another clinical trial"}
• {"criterion_text":"- Medullary thyroid cancer"}
• {"criterion_text":"- Pancreatic cancer"}
• {"criterion_text":"- Body mass index (BMI) >40 kg/m2"}
• {"criterion_text":"- A clinical condition requiring surgical treatment of coronary artery disease"}
• {"criterion_text":"- Pregnancy/lactation"}
• {"criterion_text":"- Other known contraindications to treatment with metformin, dapagliflozin or semaglutide"}
• {"criterion_text":"- Condition after coronary artery bypass surgery"}
• {"criterion_text":"- Diagnosed diabetes or Hba1c>6.5 mg% at the time of screening/randomization visit"}
• {"criterion_text":"- Other serious illnesses requiring planned hospital treatment during the examination"}

Primary endpoints

• {"endpoint_text":"- The impact of GLP-1 analogue treatment on the progression of coronary artery disease (expressed as a change in the % change in the volume of non-calcified atherosclerotic plaque in CT assessed by coronary CT) in relation to routine treatment (intention-to-treat);","definition_or_measurement_approach":"Change in % volume of non-calcified atherosclerotic plaque assessed by coronary CT (CCTA) over observation time (24 months); analyzed intention-to-treat."}
• {"endpoint_text":"- The impact of flozin treatment on the progression of coronary artery disease (expressed as a change in the % change in the volume of non-calcified atherosclerotic plaque at heart rate assessed in coronary CT) in relation to routine treatment (intention-to-treat);","definition_or_measurement_approach":"Change in % volume of non-calcified atherosclerotic plaque assessed by coronary CT (CCTA) over observation time (24 months); analyzed intention-to-treat."}

Secondary endpoints

• {"endpoint_text":"- The effect of each of the tested drugs vs. the control group on the progression of coronary artery disease (expressed as a change in the % change in the volume of uncalcified atherosclerotic plaque in t.w. assessed in coronary CT) (as treated);","definition_or_measurement_approach":"Change in % volume of uncalcified atherosclerotic plaque assessed by coronary CT; as-treated analysis."}
• {"endpoint_text":"- Comparison of the effect of semaglutide vs. flozin on the progression of coronary artery disease (expressed as a change in the % change in the volume of uncalcified atherosclerotic plaque at heart rate assessed by coronary CT scan)(intention to treat/as treated);","definition_or_measurement_approach":"Comparison of % change in uncalcified plaque volume by coronary CT; intention-to-treat and as-treated analyses."}
• {"endpoint_text":"- The effect of each of the tested drugs vs. the control group/comparison of the effect of semaglutide vs. flozin on the progression of coronary artery disease (expressed as a % change in the volume of the entire atherosclerotic plaque in t.w. assessed in coronary CT); (intention to treat/as treated)","definition_or_measurement_approach":"Change in % volume of entire atherosclerotic plaque assessed by coronary CT; intention-to-treat and as-treated."}
• {"endpoint_text":"- The effect of each of the tested drugs vs. the control group/comparison of the effect of semaglutide vs flozin on the progression of coronary artery disease (expressed as a % change in the volume of individual components of the atherosclerotic plaque in CT assessed in coronary CT); (intention to treat/as treated);","definition_or_measurement_approach":"Change in % volume of plaque components (e.g., necrotic core, fibrous tissue) by coronary CT; intention-to-treat and as-treated."}
• {"endpoint_text":"- Assessment of the effect of each of the studied drugs vs. the control group/comparison of the effect of semaglutide vs. flozin on the progression of coronary artery disease (expressed as the conversion of non-calcified plaque into calcified plaque in CT assessed in coronary CT); (intention to treat/as treated);","definition_or_measurement_approach":"Conversion rate of non-calcified to calcified plaque assessed by coronary CT; intention-to-treat and as-treated."}
• {"endpoint_text":"- Assessment of the impact of individual tested drugs vs. the control group/comparison of the effect of semaglutide vs. flozin on the risk of SN expressed as the dynamics of high-risk features 1. Change in the number of high-risk atherosclerotic lesions defined as the presence of at least 2 high-risk features among: spotty calcifications, low attenuation plaque, i.e. plaque density < 30 HU, positive remodeling, napkin ring sign assessed in koro-CT 2. Change in Pericoronary FAI assessed in koro-CT","definition_or_measurement_approach":"Change in number of high-risk lesion features (as defined) and change in Pericoronary Fat Attenuation Index (FAI) measured on coronary CT."}
• {"endpoint_text":"- Evaluation of weight change, including body composition, in patients treated with semaglutide vs. patients treated with flozin - weight - body mass index (BMI). - fat mass - skeletal muscle mass - Fat-To-Muscle Ratio (FMR). - Body Cell Mass (BCM) - Visceral Fat Area (VFA","definition_or_measurement_approach":"Assessment of weight and body composition metrics (weight, BMI, fat mass, skeletal muscle mass, FMR, BCM, VFA) between treatment groups."}
• {"endpoint_text":"- Evaluation of waist-to-hip index (WHI) change in patients treated with semaglutide vs. patients treated with phlorizin","definition_or_measurement_approach":"Change in waist-to-hip index compared between groups."}
• {"endpoint_text":"- Evaluation of change in inflammatory parameters in patients treated with semaglutide vs. patients treated with phlorizin. Concentration of hsCRP","definition_or_measurement_approach":"Change in hsCRP concentration compared between groups."}
• {"endpoint_text":"- Evaluation of change in lipid levels in patients treated with semaglutide vs. patients treated with flozin. - total cholesterol - low-density lipoproteins (LDL) - high-density lipoproteins (HDL) - non-HDL cholesterol - triglycerides - lipoprotein A","definition_or_measurement_approach":"Changes in lipid panel components (total cholesterol, LDL, HDL, non-HDL, triglycerides, Lp(a)) compared between groups."}
• {"endpoint_text":"- Evaluation of change in the percentage of glycated hemoglobin (HBA1c) in patients treated with semaglutide vs. patients treated with flozin","definition_or_measurement_approach":"Change in HbA1c percentage compared between groups."}
• {"endpoint_text":"- Evaluation of change in the percentage of patients with normal blood pressure in patients treated with semaglutide vs. patients treated with flozin. Change in percentage of patients with normal blood pressure defined as systolic pressure <140 mmHg and diastolic pressure <90 mmHg","definition_or_measurement_approach":"Change in proportion of patients meeting BP criteria (SBP <140 and DBP <90) between groups."}
• {"endpoint_text":"- Change in the percentage of patients who smoke tobacco","definition_or_measurement_approach":"Change in percentage of patients reporting tobacco use between baseline and follow-up."}
• {"endpoint_text":"- Evaluation of compliance with physical activity recommendations in patients treated with semaglutide vs. patients treated with flozin. - Percentage of patients classified in the \"high\" physical activity category; - Percentage of patients classified in the \"sufficient\" physical activity category; - Percentage of patients classified in the \"insufficient\" physical activity category","definition_or_measurement_approach":"Proportions of patients in physical activity categories (high/sufficient/insufficient) compared between groups."}
• {"endpoint_text":"- Evaluation of dietary compliance in patients treated with semaglutide vs. patients treated with flozin. Change in the DASH Index between baseline and end of study","definition_or_measurement_approach":"Change in DASH Index score from baseline to end of study compared between groups."}
• {"endpoint_text":"- Diagnosis of diabetes based on the criteria of the Polish Diabetes Association","definition_or_measurement_approach":"Incidence of diabetes diagnosed per Polish Diabetes Association criteria."}
• {"endpoint_text":"- Evaluation of the onset of heart failure requiring hospitalization. Hospitalization for heart failure.","definition_or_measurement_approach":"Occurrence of heart failure hospitalizations."}
• {"endpoint_text":"- Number of unplanned hospitalizations","definition_or_measurement_approach":"Count of unplanned hospital admissions."}
• {"endpoint_text":"- Number of major cardiovascular events and strokes (MACCE: death/myocardial infarction/revascularization/stroke) separately and combined.","definition_or_measurement_approach":"Counts of MACCE events (death, MI, revascularization, stroke) individually and combined."}
• {"endpoint_text":"- Homeostatic Model Change Assessment – Insulin Resistance (HOMA-IR).","definition_or_measurement_approach":"Change in HOMA-IR between baseline and end of study."}
• {"endpoint_text":"- Assessment of changes in the concentration of selected oxidative stress markers.Change in concentration of selected oxidative stress markers: catalase, superoxide dismutase (SOD), Oxygen Radical Absorbance Capacity (ORAC), total antioxidant capacity (TAC)","definition_or_measurement_approach":"Change in listed oxidative stress marker concentrations (catalase, SOD, ORAC, TAC) from baseline to end of study."}

Poland

Earliest CTIS Part Ii Submission Date

13-02-2024

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

561

Number Of Sites

1

Number Of Participants

300

Primary sponsor

Full Name

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland