The effect of a single dose of SGLT2 inhibitor, empagliflozin, on oxidative stress in patients undergoing elective coronary angiography
| ISRCTN | ISRCTN11022820 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11022820 |
| Secondary identifying numbers | Croatian Science Foundation supported project studying Glycosylation in Cardiovascular Diseases UIP-2019-04-5692, BioMolTox funded by the European Union – Next Generation EU Program Contract of 8 December 2023, Class 643-02/23-01/00016, Reg. no. 533-03-23-0006 |
- Submission date
- 10/10/2025
- Registration date
- 13/10/2025
- Last edited
- 15/10/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
This study aims to investigate whether a single dose of the drug empagliflozin, given before a planned (elective) coronary angiography, can reduce oxidative stress in patients without diabetes. Oxidative stress plays a key role in the development and progression of cardiovascular disease. While empagliflozin is usually used to treat diabetes and heart failure, recent findings suggest it may also have antioxidant effects. This study will assess those effects in a clinical setting.
Who can participate?
Adults aged 18 years or older who are scheduled to undergo elective coronary angiography are eligible to participate in the study. Participants must be able to understand the study procedures and provide written informed consent. People with diabetes, advanced kidney disease, active cancer, autoimmune disease, or recent heart attacks are not eligible.
What does the study involve?
Participants will be randomly assigned to one of two groups. One group will receive a single 10 mg dose of empagliflozin before the coronary angiography; the other group will receive standard care. Blood samples will be collected before and after the procedure to measure markers of oxidative stress, DNA damage, and protein glycosylation. The study is double-blinded, meaning neither the participants nor the investigators performing analyses will know who received the drug.
What are the possible benefits and risks of participating?
There is no direct benefit to participants. However, the findings may help researchers better understand the antioxidant effects of empagliflozin and improve future patient care. Risks are minimal, as the drug is already approved and widely used in clinical practice, and blood samples are taken using standard procedures.
Where is the study run from?
The study is conducted at the Department of Cardiology, General Hospital Dr Josip Bencevic, Slavonski Brod, Croatia, in collaboration with several research institutes in Zagreb.
When is the study starting and how long is it expected to run for?
The study began in September 2023 and is expected to run for approximately 12 months.
Who is funding the study?
1. Croatian Science Foundation
2. European Union – NextGenerationEU Program
Who is the main contact?
Dr Katica Cvitkusic Lukenda, Department of Cardiology, General Hospital Dr Josip Bencevic, Slavonski Brod, Croatia, Katica.Cvitkusic-lukenda@bolnicasb.hr, kclukenda@gmail.com
Contact information
Public, Scientific, Principal investigator
Josipa Lovretica 25
Slavonski Brod
35000
Croatia
 ORCID ID |
0000-0001-6188-0708 |
|---|---|
| Phone | +385 98 556 576 |
| Katica.Cvitkusic-lukenda@bolnicasb.hr |
Study information
| Study design | Prospective randomized double-blind controlled parallel-group interventional study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Empagliflozin and oxidative stress in non-diabetic patients undergoing coronary angiography |
| Study objectives | The aim of this study is to determine whether a single dose of the SGLT2 inhibitor empagliflozin, administered before elective diagnostic coronary angiography, can reduce oxidative stress in patients. |
| Ethics approval(s) |
1. Approved 07/09/2023, Ethics Committee of General Hospital Dr. Josip Bencevic (Andrije Stampara 42, Slavonski Brod, 35000, Croatia; +385 35 201 610; bolnicasb@bolnicasb.hr), ref: URBROJ: 04000000/23-65 2. Approved 23/10/2023, Ethics Committee of the Institute for Medical Research and Occupational Health (Ksaverska cesta 2, Zagreb, 10001, Croatia; +385 1 458 2500; jmacan@imi.hr), ref: URBROJ: 100-21/23-12 3. Approved 30/11/2023, Bioethics Committee of the Ruder Boskovic Institute (Bijenicka cesta 54, Zagreb, 10000, Croatia; +385 1 456 0950; stojkov@irb.hr), ref: BROJ: BEP-5968/2-2023.lu |
| Health condition(s) or problem(s) studied | Coronary Artery Disease Oxidative Stress Angiography, Coronary Sodium-Glucose Transporter 2 Inhibitors |
| Intervention | Experimental group: Single oral dose of empagliflozin 10 mg administered approximately 2 hours before elective coronary angiography, in addition to standard premedication (e.g., anxiolytics). Control group: Standard premedication care without empagliflozin. Both groups: Venous blood samples were collected at three time points: Baseline (before coronary angiography), 4 hours after coronary angiography, 24 hours after coronary angiography. Total Antioxidant Capacity (TAC) – measured at all three time points (baseline, 4h, 24h) DNA damage assessment via alkaline comet assay – performed at all three time points IgG and total plasma protein N-glycosylation profiling – performed at baseline and 24 hours after the procedure Routine biochemical parameters: serum creatinine, estimated glomerular filtration rate (eGFR), high-sensitivity troponin I (hsTnI), and high-sensitivity C-reactive protein (hsCRP) – measured at baseline and 24 hours after coronary angiography. Randomization method: Simple randomization using a computer-generated list, with allocation performed by an independent third party. Duration of intervention: Single administration. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | This is an exploratory biomarker study assessing the effect of a single pre-procedural dose of empagliflozin on oxidative stress and glycosylation profiles in non-diabetic patients undergoing elective coronary angiography. The study is not intended to evaluate therapeutic efficacy or safety endpoints of the drug in a new indication. |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Empagliflozin |
| Primary outcome measure | Change in oxidative stress levels, measured directly using Total Antioxidant Capacity (TAC) at baseline, 4, and 24h, and indirectly using a Comet assay at baseline, 4, and 24h, and N-glycan profiling at baseline and 24 hours after coronary angiography |
| Secondary outcome measures | Changes in biochemical markers, including serum creatinine, estimated glomerular filtration rate (eGFR), high-sensitivity cardiac troponin I (hs-TnI), and high-sensitivity C-reactive protein (hsCRP), were measured using standard biochemical methods at baseline and 24 hours after coronary angiography |
| Overall study start date | 30/06/2023 |
| Completion date | 23/01/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 40 Years |
| Upper age limit | 85 Years |
| Sex | All |
| Target number of participants | 60 |
| Total final enrolment | 60 |
| Key inclusion criteria | 1. Scheduled for elective coronary angiography 2. Able to provide written informed consent |
| Key exclusion criteria | 1. Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m² 2. New York Heart Association (NYHA) class IV heart failure 3. Recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) within the past 6 months 4. Active malignancy 5. Inflammatory or autoimmune disease 6. Chronic use of SGLT2 inhibitors 7. Diagnosed diabetes mellitus 8. Heart failure with reduced ejection fraction (HFrEF) 9. Life expectancy less than 12 months |
| Date of first enrolment | 05/10/2023 |
| Date of final enrolment | 23/01/2024 |
Locations
Countries of recruitment
- Croatia
Study participating centre
Slavonski Brod
35000
Croatia
Sponsor information
Hospital/treatment centre
Andrije Štampara 42
Slavonski Brod
35000
Croatia
| Phone | +385 35 201 685 |
|---|---|
| bolnicasb@bolnicasb.hr |
Funders
Funder type
Government
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Croatian Science Foundation, The Croatian Science Foundation, HRZZ
- Location
- Croatia
Government organisation / National government
- Alternative name(s)
- Next Gen EU, European Union Recovery Instrument, Next Generation EU, NGEU
Results and Publications
| Intention to publish date | 30/11/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The dataset generated during and/or analysed during the current study will be available upon request from Katica Cvitkusic Lukenda, MD, PhD, Katica.Cvitkusic-lukenda@bolnicasb.hr, kclukenda@gmail.com. - Type of data that will be shared: Participant-level data related to oxidative stress markers (TAC, Comet assay, N-glycan profiling), biochemical results, basic demographic and clinical parameters (e.g. age, sex, comorbidities, anthropometry, blood pressure). - Timing for availability: Data will be made available upon reasonable request, following publication of the primary results. - Consent: Informed consent included a statement that data may be used for future research purposes and that all shared data will be anonymized. - Anonymization: All shared data will be fully anonymized, with no personally identifiable information included. - Ethical or legal restrictions: No additional restrictions beyond standard anonymization and ethical use of data. - Additional comments: We are committed to transparency and collaboration and will consider data sharing requests that align with ethical standards and the scope of the original consent. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other files | CONSORT flow diagram | 15/10/2025 | No | No | |
| Other files | Informed Consent Form – Croatian version | 15/10/2025 | No | No | |
| Other files | Informed Consent Form – English version | 15/10/2025 | No | No | |
| Other files | SPIRIT timeline | 15/10/2025 | No | No |
Additional files
- CONSORT_2025_flow_diagram_ISRCTN11022820.pdf
- CONSORT flow diagram
- Participant_Timeline_SPIRIT_2025_ISRCTN11022820.pdf
- SPIRIT timeline
- ISRCTN11022820 Informed Consent Form_Croatian version.pdf
- Informed Consent Form – Croatian version
- ISRCTN11022820 Informed Consent Form_English version.pdf
- Informed Consent Form – English version
Editorial Notes
15/10/2025: Additional files uploaded.
13/10/2025: Study's existence confirmed by the Ethics Committee of General Hospital Dr Josip Bencevic, Croatia.
