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NCT number NCT03398577
Study type Interventional
Source Sheba Medical Center
Contact Gal Shmukler, MA
Phone +972-3-5344703
Email Gal.Shmukler@sheba.health.gov.il
Status Not yet recruiting
Phase Phase 4
Start date February 1, 2018
Completion date December 31, 2018

Clinical Trial Summary

The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Therefore, in the present study the investigators plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.


Clinical Trial Description

Patients with ischemic heart disease and diabetes are at a particularly high risk for the recurrence of cardiovascular events, conversely, certain classes of oral anti-diabetic medications have been shown to cause hypoglycemia with adverse cardiovascular implications 1,2. Diabetes induces complex vascular changes, promoting accelerated atherosclerosis and a hyper-coagulable state, as can be assessed indirectly by a number of markers. Principal perturbations include endothelial dysfunction, increased inflammatory plaque infiltration, adhesion molecule over-expression and adverse effects of circulating fatty acids and advanced glycosylation end-products.

Cardiovascular safety of anti-diabetic medications is of paramount importance and has been under recent FDA and EDQM scrutiny. A number of hypoglycemic drugs, especially sulfonylureas, have been associated with significant hypoglycemia and adverse events induced by sympathetic activation. Activation of the sympathetic system has numerous implications, including surges of heart rate, blood pressure but also pro-inflammatory and pro-coagulant effects. This partially explains increased cardiovascular adverse events noted with these drugs. Newer classes of antidiabetic medication have recently shown improved survival outcomes in patients with cardiovascular disease, yet the exact mechanisms of the observed risk reduction are mostly yet to be elucidated 3,4. One possible mechanism is anti-inflammatory effect exerted directly or indirectly by SGLT2I or diuretic effect leading to left ventricular unloading with NT pro BNP level reduction.

The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Reduction of inflammatory marker levels is of great clinical importance and has been shown to correlate with reduction in significant clinical events5. Therefore, in the present study we plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.

Key representative markers for the present study are chosen in order to correctly represent alterations in: inflammation (hs-CRP, IL(interleukin) -1 beta, IL-6, P-Selectin, TNF-alfa), and LV strain (NT pro BNP).

The effect of SGLT2I on the above-mentioned parameters has not been studied in humans. Accordingly, the demonstration of significant improvements in markers of athero-thrombosis and inflammation in high-risk diabetic patients is of great clinical importance and novelty that may be employed for the reduction of major cardiovascular events in this population.

Importantly, the effects of SGLT2I therapy will be evaluated in a prospective controlled clinical trial in a closely supervised cardiac rehabilitation setting, which includes lifestyle changes, regular, quantifiable physical activity, and predefined nutritional interventions.


Study Design


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