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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04806633
• Other study ID #: 2663
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 1, 2021
• Est. completion date: December 1, 2023

Study information

• Verified date: March 2021
• Source: G.Gennimatas General Hospital
• Contact: Spyridon Deftereos, Prof.
• Email: spdeftereos[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1722
• Est. completion date: December 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dapagliflozin 5mg
Patients randomized in this arm will receive dapagliflozin at a dose of 5mg once daily.
• Placebo
Patients randomized in this arm will receive placebo.

Locations

Country	Name	City	State
Greece	2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.	Athens
Greece	Cardiology Department, Athens General Hospital "G. Gennimatas"	Athens

Sponsors (2)

Lead Sponsor	Collaborator
G.Gennimatas General Hospital	2nd Department of Cardiology, "Attikon" University Hospital, National and Kapodistrian University of Athens

Country where clinical trial is conducted

Greece, 

References & Publications (7)

Aurelio A, Durante A. Contrast-induced nephropathy in percutaneous coronary interventions: pathogenesis, risk factors, outcome, prevention and treatment. Cardiology. 2014;128(1):62-72. doi: 10.1159/000358042. Epub 2014 Feb 18. Review. — View Citation

Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70. Epub 2005 Sep 21. — View Citation

Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 Inhibitors and the Diabetic Kidney. Diabetes Care. 2016 Aug;39 Suppl 2:S165-71. doi: 10.2337/dcS15-3006. — View Citation

Garofalo C, Borrelli S, Liberti ME, Andreucci M, Conte G, Minutolo R, Provenzano M, De Nicola L. SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects. Medicina (Kaunas). 2019 Jun 11;55(6). pii: E268. doi: 10.3390/medicina55060268. Review. — View Citation

Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic — View Citation

Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. Horm Metab Res. 2016 — View Citation

McCullough PA, Choi JP, Feghali GA, Schussler JM, Stoler RM, Vallabahn RC, Mehta A. Contrast-Induced Acute Kidney Injury. J Am Coll Cardiol. 2016 Sep 27;68(13):1465-1473. doi: 10.1016/j.jacc.2016.05.099. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence (cases per 100 patient-years) of hypoglycemia in both arms Any episode of hypoglycemia defined as serum glucose 60< mg/dl associated with symptoms of hypoglycemia.		1 month
Other	Incidence (cases per 100 patient-years)of diabetic ketoacidosis.	Any episode of metabolic acidosis (pH<7.3) with decreased serum bicarbonate (<18mEq/ml) and	1 month
Other	Incidence (cases per 100 patient-years)of lower urinary tract infections		1 month
Other	Comparison of all cause mortality between the two groups		1 month
Primary	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	Development of at least Stage 2 AKI (according to the KDIGO criteria), i.e. Increase in sCR>2.0-fold from baseline.		1 month