Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention
Primary Purpose
Left Cardiac Catheterization, Percutaneous Coronary Intervention, Acute Kidney Injury
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Greece
Study Type
Interventional
Intervention
Dapagliflozin 5mg
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Left Cardiac Catheterization focused on measuring dapaglifozin, iodinated contrast media, Sodium-glucose Co-transporter 2 Inhibitors, Acute Kidney Injury
Eligibility Criteria
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.
Sites / Locations
- Cardiology Department, Athens General Hospital "G. Gennimatas"
- 2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Dapagliflozin
Placebo
Arm Description
Patients who will be randomized to receive dapagliflozin following cardiac catheterization and PCI
Patients who will be randomized to receive placebo following cardiac catheterization and PCI
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Development of at least Stage 2 AKI (according to the KDIGO criteria), i.e. Increase in sCR>2.0-fold from baseline.
Full Information
NCT ID
NCT04806633
First Posted
March 17, 2021
Last Updated
March 18, 2021
Sponsor
G.Gennimatas General Hospital
Collaborators
2nd Department of Cardiology, "Attikon" University Hospital, National and Kapodistrian University of Athens
1. Study Identification
Unique Protocol Identification Number
NCT04806633
Brief Title
Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention
Official Title
Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2021 (Anticipated)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
G.Gennimatas General Hospital
Collaborators
2nd Department of Cardiology, "Attikon" University Hospital, National and Kapodistrian University of Athens
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1722 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dapagliflozin
Arm Type
Active Comparator
Arm Description
Patients who will be randomized to receive dapagliflozin following cardiac catheterization and PCI
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients who will be randomized to receive placebo following cardiac catheterization and PCI
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 5mg
Intervention Description
Patients randomized in this arm will receive dapagliflozin at a dose of 5mg once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients randomized in this arm will receive placebo.
Primary Outcome Measure Information:
Title
Comparison of incidence of acute kidney injury (AKI) between the two study arms
Description
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.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Development of at least Stage 2 AKI (according to the KDIGO criteria), i.e. Increase in sCR>2.0-fold from baseline.
Time Frame
1 month
Other Pre-specified Outcome Measures:
Title
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.
Time Frame
1 month
Title
Incidence (cases per 100 patient-years)of diabetic ketoacidosis.
Description
Any episode of metabolic acidosis (pH<7.3) with decreased serum bicarbonate (<18mEq/ml) and
Time Frame
1 month
Title
Incidence (cases per 100 patient-years)of lower urinary tract infections
Time Frame
1 month
Title
Comparison of all cause mortality between the two groups
Time Frame
1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Spyridon Deftereos, Prof.
Email
spdeftereos@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Georgios Giannopoulos, Prof.
Phone
+302107768132
Email
georgios.giannopolous@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Spyridon Deftereos, Prof.
Organizational Affiliation
2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiology Department, Athens General Hospital "G. Gennimatas"
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
City
Athens
ZIP/Postal Code
12462
Country
Greece
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24557146
Citation
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.
Results Reference
result
PubMed Identifier
31212638
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):268. doi: 10.3390/medicina55060268.
Results Reference
result
PubMed Identifier
27659469
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.
Results Reference
result
PubMed Identifier
16177006
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. doi: 10.1681/ASN.2004090740. Epub 2005 Sep 21.
Results Reference
result
PubMed Identifier
32970396
Citation
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.
Results Reference
result
PubMed Identifier
26158396
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 Mar;48(3):191-5. doi: 10.1055/s-0035-1555791. Epub 2015 Jul 9.
Results Reference
result
PubMed Identifier
27440829
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.
Results Reference
result
Learn more about this trial
Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention
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