Using SGLT2 inhibitors to prevent heart rhythm issues and kidney injury before heart surgery

SGLT2 Inhibitor TrEatment iN Patients Awaiting cOronary arTery bYpass Surgery to Reduce Post-opErative Atrial Fibrillation and Kidney Injury (STENOTYPE Trial)

This study is testing if a medication called dapagliflozin can help prevent heart rhythm problems and kidney issues in patients with chronic coronary syndrome who are about to have heart surgery.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Region Örebro County (Academic / other)
• Locations: 8 sites (Brno and 7 other locations)
• Trial ID: NCT05852704 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates whether administering dapagliflozin, an SGLT2 inhibitor, can reduce the incidence of post-operative atrial fibrillation and acute kidney injury in patients with chronic coronary syndrome awaiting coronary artery bypass surgery (CABG). The study is a multicenter, randomized, double-blinded, controlled trial involving 800 participants who will receive either dapagliflozin or a placebo for at least seven days prior to surgery. The primary endpoint is the occurrence of new onset atrial fibrillation during hospitalization after CABG, while secondary endpoints include the incidence of acute kidney injury. Participants will be monitored for safety and outcomes through national registries for up to 12 months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with chronic coronary syndrome scheduled for elective CABG surgery.

Not a fit: Patients with type 1 diabetes, recent SGLT2 inhibitor treatment, or certain heart conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of post-operative complications such as atrial fibrillation and acute kidney injury in patients undergoing heart surgery.

How similar studies have performed: Other studies have shown promising results with SGLT2 inhibitors in similar contexts, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Written informed consent.
* Patients aged 18 years or older.
* Chronic coronary syndrome scheduled for elective isolated CABG surgery with extra corporeal circulation, or elective CABG surgery with extra corporeal circulation combined with aortic valve replacement, mitral valve surgery, and / or aortic root surgery.

Exclusion Criteria:

* Treatment with an SGLT2 inhibitor within 8 weeks prior to enrolment or planned treatment.
* Intolerance, hypersensitivity, or other contraindications of dapagliflozin.
* Type 1 diabetes mellitus.
* Symptomatic hypotension or systolic blood pressure \<95 mmHg at two out of three measurements at enrolment.
* Current acute decompensated heart failure or hospitalization due to decompensated heart failure \<4 weeks prior to enrolment.
* Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic cardiomyopathy.
* Implantation or intent to implant a cardiac resynchronization device within 12 weeks prior to enrolment.
* Stroke or transient ischemic attack within 12 weeks prior to enrolment.
* Symptomatic bradycardia or second or third-degree atrioventricular block without pacemaker treatment.
* Any condition such as, but not limited to, malignancy, with a life expectancy of \<2 years based on the investigator's clinical judgement.
* Hepatic impairment (aspartate transaminase or alanine transaminase \>3 × the upper limit of normal, or total bilirubin \>2 × upper limit of normal at the time of enrolment).
* Severe (estimated glomerular filtration rate \< 25 mL/min/1.73 m2), unstable, or rapidly progressing renal disease at the time of enrolment.
* CABG surgery planned within one week.
* Emergency surgery with hemodynamic instability.
* Previous history of AF.
* Women of childbearing potential (i.e., those who are fertile, following menarche and until becoming post-menopausal, unless permanently sterile\*)

  1. 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
  2. Who have a positive pregnancy test at enrolment or randomization, OR
  3. Who are breast-feeding.
* Participation or recent participation in a clinical trial with an investigational medicinal product within 30 days before randomization.
* Previous randomization in the STENOTYPE trial.
* Previous (within 30 days) or concomitant participation in another clinical trial with an investigational product. Registries and observational studies are allowed.
* 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.

Where this trial is running

Brno and 7 other locations

• St. Anne University Hospital — Brno, Czechia (Not_yet_recruiting)
• Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark — Aarhus, Denmark (Recruiting)
• Department of Cardiothoracic Surgery, Kobenhavn — Copenhagen, Denmark (Not_yet_recruiting)
• Odense University Hospital — Odense, Denmark (Not_yet_recruiting)
• Sahlgrenska University Hospital — Gothenburg, Sweden (Recruiting)
• Linköping University Hospital — Linköping, Sweden (Not_yet_recruiting)
• Skane University Hospital — Lund, Sweden (Recruiting)
• Department of cardiology — Örebro, Sweden (Recruiting)

Study contacts

• Principal investigator: Anna Björkenheim, MD, PhD — VO Hjärt- lungmedicin och klinisk fysiologi USÖ
• Study coordinator: Anna Björkenheim, MD, PhD

Conditions Chronic Coronary Syndrome; Atrial Fibrillation; Atrial fibrillation; Acute Kidney Injury; Coronary artery bypass grafting