Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention

Study Overview
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Brief Summary
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Left heart catheterization and percutaneous coronary intervention (PCI) has become a useful tool in interventional cardiology, in which iodinated contrast media is used. Although the use of iodinated contrast media (CM) is considered to be safe in patients with normal renal function, it is risky in patients with known chronic renal insufficiency (CKD) and diabetes mellitus. Contrast induced nephropathy (CIN) remains one of the most leading causes of in hospital acute kidney injury (AKI), affecting morbidity and mortality. There are various mechanisms through which CM develop their nephrotoxic effects, including renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. Inhibitors of type 2 sodium- glucose co-transporter (SGLT2i) is a relatively recent addition to the array of anti-diabetic agents, becoming part of everyday clinical practice. However, although SGLT2i were first used solely as antidiabetics because of their glycosuric effect, further research demonstrated that these drugs may independently reduce cardiovascular events, especially in patients with heart failure, a benefit that was consistent among diabetic and non-diabetic patients. Moreover, pleiotropic effects have been observed, including a reno-protective action. In addition to the effects mediated by intrarenal hemodynamic changes, SGLT2-i also have direct anti-inflammatory and antifibrotic nephroprotective effects. Indeed, SGLT2-i suppress the production of reactive oxygen species, lessening glomerulosclerosis and tubulo-interstitial fibrosis. These findings suggest that the use of SGLT2i could offer benefit by reducing/ preventing the nephrotoxic effects of contrast media leading to the assumption that the use of these drugs could prevent the incidence nephropathy after cardiac catheterization and percutaneous coronary intervention.

Official Title
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Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention

Conditions
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Left Cardiac Catheterization, Percutaneous Coronary Intervention, Acute Kidney Injury, Sodium-glucose Co-transporter 2 Inhibitors

Intervention / Treatment
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* Drug: Dapagliflozin 5mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>18 years Written informed consent Glomerular Filtration Rate (GFR)≥ 30 ml/min/1.73m2 [CKD stage G1-G3] Percutaneous coronary intervention in patients with NSTEMI, UA, STCD and asymptomatic patients Exclusion Criteria: Active malignancy Participation in other intervention study Class I or equivalent indication for treatment with a SGLT2 inhibitor Pregnancy or willing of pregnancy during the follow up period Active urogenital infection Diabetes mellitus type 1 History of diabetic ketoacidosis Cardiogenic shock eGFR < 29 ml/min/1.73m2 Patients with an indication for SGLT2 inhibitor will be included in a prospective registry. Their treatment will be determined by their attending physicians.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin<br>Patients who will be randomized to receive dapagliflozin following cardiac catheterization and PCI | Drug: Dapagliflozin 5mg<br>* Patients randomized in this arm will receive dapagliflozin at a dose of 5mg once daily.<br>|
| Placebo Comparator: Placebo<br>Patients who will be randomized to receive placebo following cardiac catheterization and PCI | Drug: Placebo<br>* Patients randomized in this arm will receive placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of incidence of acute kidney injury (AKI) between the two study arms | AKI is defined defined as an absolute creatinine level increase of at least 0.3 mg/dL (≥26.5 μmol/L) or at least 1.5-fold from baseline. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of at least Stage 2 AKI (according to the KDIGO criteria), i.e. Increase in sCR>2.0-fold from baseline. |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dapaglifozin, iodinated contrast media, Sodium-glucose Co-transporter 2 Inhibitors, Acute Kidney Injury