E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronary macrovascular and microvascular function of type 2 diabetic patients with stable coronary artery disease and acute coronary syndrome (excluding ST elevation myocardial infarction).
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E.1.1.1 | Medical condition in easily understood language |
Coronary function of type 2 diabetic patients with stable coronary artery disease and acute coronary syndrome (excluding ST elevation myocardial infarction).
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effects of dapagliflozin [sodium-glucose linked transporter 2 (SGLT2) inhibitor] on: 1. The coronary flow reserve (CFR) 2. The physiology of coronary macrocirculation (epicardial coronary segments), as measured by fractional flow reserve (FFR) 3. The physiology of the coronary microcirculation, as measured by the index of microvascular resistance (IMR). in T2DM patients with stable CAD or ACS (excluding STEMI) referred for coronary angiography. For NSTEMI or unstable angina ACS patients, the non-culprit vessels will be interrogated.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. T2DM patients presenting with stable angina and a clinical indication for cardiac catheterization 2. T2DM patients with NSTEMI or unstable angina referred for cardiac catheterization 3. Demonstration of coronary lesion(s) with non-significant fractional flow reserve (FFR) values (>0.80), for which revascularisation is deferred 4. Agreement to practice an acceptable method of birth control for women of childbearing potential 5. Signed patient informed consent
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E.4 | Principal exclusion criteria |
1. Age < 18 years old 2. Pregnancy or breastfeeding 3. Body mass index ≥45 kg/m2. 4. Creatinine clearance ≤45 ml/min/1.73 m2 (as calculated by MDRD formula for estimated GFR). 5. Indication of liver disease, defined by serum levels of alanine amininotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal during screening or run-in phase 6. Uncontrolled hyperglycemia with glucose >240 mg/dL after an overnight fast 7. Stroke, or transient ischemic attack within 2 months prior to informed consent 8. 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 9. Any uncontrolled endocrine disorder except type 2 diabetes 10. Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent 11. Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body weight 12. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 2 years 13. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells 14. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption 15. Planned cardiac surgery or angioplasty within 3 months 16. Any clinical condition that would jeopardize patient safety while participating in this clinical trial (in Canada, this included current genito-urinal infection or genito-urinal infection within 2 weeks prior to informed consent) 17. Life expectancy < 3 years
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective is to determine the effects of dapaglifozin and the standard of care on the longitudinal change of CFR, FFR and IMR. The longitudinal change (Δ) is defined as the value at follow-up (6 months) minus the value at baseline. Comparisons between the study arms, using the standard of care as a comparator will be made, in order to explore the relative effect of drugs on the physiology of the coronary macro and microcirculation.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after enrolment in the study. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Explore the impact of dapaglifozin on the coronary and microcirculatory function of type 2 diabetic patients |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |