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

NCT04806633 | Unknown Early Phase 1

• 1 other identifier: 2663
• Study Type: interventional
• Target: 1,722
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Keywords

dapaglifozin; iodinated contrast media; Sodium-glucose Co-transporter 2 Inhibitors; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Development of at least Stage 2 AKI (according to the KDIGO criteria), i.e. Increase in sCR>2.0-fold from baseline.

  1 month

Other Outcomes (4)

• 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

• Incidence (cases per 100 patient-years)of diabetic ketoacidosis.

  1 month

• Incidence (cases per 100 patient-years)of lower urinary tract infections

  1 month

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Patients who will be randomized to receive dapagliflozin following cardiac catheterization and PCI

Drug: Dapagliflozin 5mg

Placebo

PLACEBO COMPARATOR

Patients who will be randomized to receive placebo following cardiac catheterization and PCI

Drug: Placebo

Interventions

Dapagliflozin 5mg DRUG

Patients randomized in this arm will receive dapagliflozin at a dose of 5mg once daily.

Dapagliflozin

Placebo DRUG

Patients randomized in this arm will receive placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• G.Gennimatas General Hospital: lead
• Attikon Hospital: collaborator

Study Sites (2)

Cardiology Department, Athens General Hospital "G. Gennimatas"

Athens, 11527, Greece

Location

2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.

Athens, 12462, Greece

Location

Related 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.

  PMID: 24557146 RESULT

• 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):268. doi: 10.3390/medicina55060268.

  PMID: 31212638 RESULT

• 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.

  PMID: 27659469 RESULT

• 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. doi: 10.1681/ASN.2004090740. Epub 2005 Sep 21.

  PMID: 16177006 RESULT

• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.

  PMID: 32970396 RESULT

• 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 Mar;48(3):191-5. doi: 10.1055/s-0035-1555791. Epub 2015 Jul 9.

  PMID: 26158396 RESULT

• 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.

  PMID: 27440829 RESULT

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Spyridon Deftereos, Prof.

  2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Spyridon Deftereos, Prof.

CONTACT

spdeftereos@gmail.com

Georgios Giannopoulos, Prof.

CONTACT

+302107768132; georgios.giannopolous@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 19, 2021
• Study Start: April 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 19, 2021

Record last verified: 2021-03

Locations

GR (2)