SGLT2 Inhibitor TrEatment iN Patients Awaiting cOronary arTery bYpass Surgery to Reduce Post-opErative Atrial Fibrillation and Kidney Injury (STENOTYPE Trial)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 8
- 主要终点
- Incidence of new onset post-operative atrial fibrillation of at least 30 seconds
研究概览
简要总结
The goal of this randomized, double-blinded, controlled clinical trial is to investigate if treatment with an sodium-glucose cotransporter-2 inhibitor (SGLT2) during the unique time window before coronary artery bypass surgery (CABG), can reduce the incidence of post-operative atrial fibrillation and/or acute kidney injury in patients with chronic coronary syndrome. The main questions it aims to answer are:
- Does treatment with an SGLT2 inhibitor during the waiting time and stable post-operative period, in patients with chronic coronary syndrome scheduled for CABG, reduce the risk of new onset atrial fibrillation compared to placebo?
- Does treatment with an SGLT2 inhibitor during the waiting time and stable post-operative period, in patients with chronic coronary syndrome scheduled for CABG, reduce the risk of acute kidney injury before hospital discharge compared to placebo?
Participants will be administered dapagliflozin 10 mg once daily or placebo for a minimum of seven days while awaiting scheduled CABG and up until discharge, with a short interruption for surgery. The active arm will be compared to the placebo arm to see if dapagliflozin can reduce the incidence of post-operative atrial fibrillation and/or acute kidney injury.
详细描述
Study centers: Up to 7 centers in Sweden, Denmark, and the Czech Republic.
Phase of development: III.
Objectives: In a multicenter, prospective, randomized, controlled clinical trial to compare dapagliflozin 10 mg once daily and placebo in preventing post-operative atrial fibrillation (AF) and acute kidney injury (AKI) in patients with chronic coronary syndrome undergoing coronary artery bypass surgery (CABG).
Methodology: Following informed consent, 800 participants are randomized in a 1:1 fashion to the intervention arm receiving a 10 mg tablet of dapagliflozin once daily and the comparator arm receiving a placebo tablet once daily for a minimum of 1 week while awaiting scheduled CABG surgery. Treatment will be terminated at the time of discharge from hospital after CABG surgery. Aside from a follow-up telephone call one week after discharge to collect safety data-and an on-site visit for type 2 diabetes patients-no extra monitoring or visits are included in the trial. Patients will be followed up 30 days and 12 months through national registries.
Primary endpoint: Incidence of new onset post-operative AF during hospitalization following CABG surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators and outcomes assessors are all blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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*)
- •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
- •Who have a positive pregnancy test at enrolment or randomization, OR
- •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.
研究组 & 干预措施
Active arm
Treatment with dapagliflozin 10 mg once daily.
干预措施: Dapagliflozin 10mg Tab (Drug)
Placebo arm
Treatment with matching placebo once daily.
干预措施: Placebo Tab (Drug)
结局指标
主要结局
Incidence of new onset post-operative atrial fibrillation of at least 30 seconds
时间窗: From CABG to discharge post-operatively up to four weeks
ECG or telemetry
次要结局
- Ventricular arrhythmias(From CABG to discharge post-operatively up to four weeks)
- New onset heart failure(From CABG to discharge post-operatively up to four weeks)
- Stroke(12 months after CABG surgery)
- Treatment of AF with amiodarone(From CABG to discharge post-operatively up to four weeks)
- Change in cardiac biomarkers(Baseline and 3 days after CABG surgery)
- Length of hospital stay(From CABG to discharge post-operatively up to four weeks)
- Length of intensive care unit stay(From CABG to discharge from intensive care unit up to four weeks)
- Mortality(30 days after CABG surgery)
- Acute kidney injury(From CABG to discharge post-operatively up to four weeks)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Start of treatment until one-week post-discharge up to 26 weeks)
- All-cause mortality(From CABG to discharge post-operatively up to four weeks)
- Treatment of AF with electrical cardioversion(From CABG to discharge post-operatively up to four weeks)
- Change in inflammatory biomarkers(Baseline and 3 days after CABG surgery)
- Change in glycated haemoglobin(Baseline and 3 days after CABG surgery)
- All-cause death(12 months after CABG surgery)
- Myocardial infarction(12 months after CABG surgery)
- Hospital admission with atrial fibrillation, heart failure, or dialysis treatment(12 months after CABG surgery)