SGLT2 inhibitor TrEatment iN patients awaiting cOronary arTery bYpass surgery to reduce Post-opErative atrial fibrillation and kidney injury (STENOTYPE trial).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Oerebro Laen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

4 Apr 2024 → ongoing

Decision date (initial)

2024-07-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hjärt-Lungfonden · Nyckelfonden Region Örebro län · The Swedish Research Council

External identifiers

EU CT number

2023-505375-75-00

ClinicalTrials.gov

NCT05852704

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To establish the efficacy of dapagliflozin in reducing the incidence of new onset post-operative AF during hospitalization following CABG.

Secondary objectives 17

1. Key secondary endpoint: 1. AKI, as defined by at least a 1.5-fold increase from baseline in serum creatinine within the prior seven days, an absolute increase in serum creatinine of 26.5 µmol/L or more within 48 hours, or a urine volume of less than 0.5 mL/kg/h for at least six hours, following Kidney Disease Improving Global Outcomes grade 1 or above). This condition is monitored in-hospital after CABG surgery.
2. Safety endpoint: 1. Safety and tolerability of dapagliflozin. Reported AEs, SAEs, and SUSAR from start of treatment until one-week post-discharge.
3. Other secondary endpoints during hospitalization after CABG surgery include: 1. All-cause mortality.
4. 2. Stroke.
5. 3. New onset heart failure.
6. 4. Ventricular arrhythmia.
7. 5. Electrical cardioversion for AF.
8. 6. Use of amiodarone for AF.
9. 7. Change in inflammatory and cardiac biomarkers from baseline to three days after CABG surgery.
10. 8. Change in HbA1c from baseline to three days after CABG surgery.
11. 9. Length of intensive care unit and hospital stay.
12. Secondary endpoints after hospital discharge include: 1. 30-day all-cause mortality.
13. 2. 12-month all-cause mortality
14. 3. 12-month myocardial infarction.
15. 4. 12-month stroke.
16. 5. 12-month hospital admission for AF or heart failure.
17. 6. 12-month dialysis treatment.

Conditions and MedDRA coding

Onset of Atrial Fibrillation and Acute Kidney Injury after coronary artery bypass surgery (CABG)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1) The subject has given their written consent to participate in the trial.
2. 2) Subject is ≥18 years at the time of written consent.
3. 3) Chronic coronary syndrome documented by coronary angiography, scheduled for CABG surgery with extra corporeal circulation. OR Patients with chronic coronary syndrome scheduled for CABG surgery with extra corporeal circulation and aortic valve replacement with extra corporeal circulation. AND/OR Patients with chronic coronary syndrome scheduled for CABG surgery with extra corporeal circulation and mitral valve replacement or repair with extra corporeal circulation. AND/OR Patients with chronic coronary syndrome scheduled for CABG surgery with extra corporeal circulation and aortic root surgery with extra corporeal circulation.

Exclusion criteria 20

1. 1) Treatment with an SGLT2 inhibitor within 8 weeks prior to enrolment or planned treatment.
2. 2) Intolerance, hypersensitivity, or other contraindications of dapagliflozin.
3. 3) Type 1 diabetes mellitus.
4. 4) Symptomatic hypotension or systolic blood pressure <95 mmHg at two out of three measurements at enrolment.
5. 5) Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.
6. 6) Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic cardiomyopathy.
7. 7) Implantation or intent to implant a cardiac resynchronization device within 12 weeks prior to enrolment.
8. 8) Stroke or transient ischemic attack within 12 weeks prior to enrolment.
9. 9) Symptomatic bradycardia or second or third-degree atrioventricular block without pacemaker treatment.
10. 10) Any condition such as, but not limited to, malignancy, with a life expectancy of <2 years based on the investigator’s clinical judgement.
11. 11) Known hepatic impairment.
12. 12) Severe (estimated GFR < 25 mL/min/1.73 m2), unstable, or rapidly progressing renal disease at the time of enrolment.
13. 13) CABG surgery planned within one week
14. 14) Emergency surgery with hemodynamic instability.
15. 15) Previous history of AF.
16. 16) Women of childbearing potential (i.e., those who are fertile, following menarche and until becoming post-menopausal, unless permanently sterile*) a. Who are not willing to use a highly effective method of contraception** judged by the investigator, from the time of signing the informed consent throughout the trial and 4 weeks thereafter, OR b. Who have a positive pregnancy test at enrolment or randomization, OR c. Who are breast-feeding.
17. 17) Participation or recent participation in a clinical trial with an IMP within 30 days before randomization.
18. 18) Previous randomization in the STENOTYPE trial.
19. 19) Previous (within 30 days) or concomitant participation in another clinical trial with an investigational product. Registries and observational studies are allowed.
20. 20) Mental inability, reluctance, or language difficulties of the subject, in the opinion of the investigator, that result in difficulty in understanding the meaning of participation in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AF lasting at least 30 seconds as detected on ECG or telemetry in-hospital after CABG surgery.

Secondary endpoints 17

1. AKI, as defined by at least a 1.5-fold increase from baseline in serum creatinine within the prior seven days, an absolute increase in serum creatinine of 26.5 µmol/L or more within 48 hours, or a urine volume of less than 0.5 mL/kg/h for at least six hours, following Kidney Disease Improving Global Outcomes grade 1 or above. This condition is monitored in-hospital after CABG surgery.
2. Safety and tolerability of dapagliflozin. Reported AEs, SAEs, and SUSAR from start of treatment until one-week post-discharge.
3. All-cause mortality.
4. Stroke.
5. New onset heart failure.
6. Ventricular arrhythmia.
7. Electrical cardioversion for AF.
8. Use of amiodarone for AF.
9. Change in inflammatory and cardiac biomarkers from baseline to end of CABG surgery, 6±2 hours, 12±2 hours, and three days after CABG surgery.
10. Change in HbA1c from baseline to three days after CABG surgery.
11. Length of intensive care unit and hospital stay.
12. 30-day all-cause mortality.
13. 12-month all-cause mortality
14. 12-month myocardial infarction.
15. 12-month stroke.
16. 12-month hospital admission for AF or heart failure.
17. 12-month dialysis treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Oerebro Laen

Sponsor organisation

Region Oerebro Laen

Address

Sodra Grev Rosengatan

City

Orebro

Postcode

701 85

Country

Sweden

Scientific contact point

Organisation

Region Oerebro Laen

Contact name

Anna Björkenheim

Public contact point

Organisation

Region Oerebro Laen

Contact name

Anna Björkenheim

Third parties 1

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications