IVABRADINE for Myocardial injury after noncardiac surgery

Inclusion criteria

• {"criterion_text":"- Undergoing noncardiac surgery"}
• {"criterion_text":"- ≥45 years of age"}
• {"criterion_text":"- Expected to require at least an overnight hospital stay after surgery"}
• {"criterion_text":"- Written informed consent to participate in the PREVENT-MINS Trial provided"}
• {"criterion_text":"- Fulfil ≥1 of the following 5 criteria (A-E): A. Current or prior history of coronary artery disease as defined by any one of the following 7 criteria: i. History of angina; ii. History of acute coronary syndrome; iii. History of a segmental cardiac wall motion abnormality on echocardiography or a segmental fixed defect on radionuclide imaging; iv. History of a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test demonstrating cardiac ischaemia; v. History of a coronary angiographic or CT coronary angiographic evidence of atherosclerotic stenosis ≥50% of the diameter of any coronary artery; vi. ECG with pathological Q waves in at least two contiguous leads; OR vii. Previous coronary artery revascularization, (i.e. percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]);"}
• {"criterion_text":"- Fulfil ≥1 of the following 5 criteria (A-E): B. Peripheral arterial disease as defined by a physician diagnosis of a current, or prior history of any of the following 4 criteria: i. Intermittent claudication; ii. Vascular surgery OR percutaneous transluminal angioplasty (PTA) for atherosclerotic disease; iii. An ankle/brachial systolic blood pressure ratio <0.90 in either leg at rest; OR iv. Angiographic, CT angiographic or doppler findings demonstrating >70% stenosis in a noncardiac artery;"}
• {"criterion_text":"- Fulfil ≥1 of the following 5 criteria (A-E): C. History of stroke as defined by any one of the following 2 criteria: i. A physician diagnosis of stroke; OR ii. CT or MRI evidence of a prior stroke;"}
• {"criterion_text":"- Fulfil ≥1 of the following 5 criteria (A-E): D. Undergoing major vascular surgery defined as all vascular surgeries (including any above foot amputation) with the exception of arteriovenous shunt, vein stripping procedures (varicose vein surgery), carotid endarterectomies, endovascular abdominal aortic aneurysm repair (EVAR); OR"}
• {"criterion_text":"- Fulfil ≥1 of the following 5 criteria (A-E): E. Any 3 of 9 risk criteria: i. Undergoing major surgery defined as: intraperitoneal, intrathoracic, retroperitoneal, or major orthopaedic; ii. History of congestive heart failure defined as a physician diagnosis of a current or prior episode of congestive heart failure OR prior radiographic evidence of vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary oedema; iii. History of a transient ischaemic attack; iv. Diabetes diagnosis and currently taking hypoglycemic agent; v. Age ≥70 years; vi. History of hypertension; vii. Serum creatinine >175 μmol/L (>2.0 mg/dl) based on the most recent values before randomisation; viii. History of smoking within 2 years of surgery; and ix. Undergoing emergent/urgent surgery, defined as surgery that a surgeon schedules to go to the operating room within 48 hours from an acute presentation to the hospital."}

Exclusion criteria

• {"criterion_text":"- Conduction abnormalities: A. Non-sinus rhythm on ECG; B. Sinoatrial or AV (2nd and 3d degree) blocks; C. Sick sinus syndrome; D. Long QT syndrome; E. Pacemaker dependent;"}
• {"criterion_text":"- Inability to tolerate oral intake"}
• {"criterion_text":"- Recent use of ivabradine (<1 month)"}
• {"criterion_text":"- Known allergy or hypersensitivity to ivabradine"}
• {"criterion_text":"- Low-risk surgical procedure based on individual physician's judgment"}
• {"criterion_text":"- Investigator considers the patient unreliable regarding requirement for study compliance"}
• {"criterion_text":"- Women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding"}
• {"criterion_text":"- Previously enrolled in the PREVENT-MINS trial"}
• {"criterion_text":"- Transplanted heart (or on waiting list)"}
• {"criterion_text":"- Use of a selected class I or III antiarrhythmic drug (quinidine, disopyramide, sotalol, ibutilide, amiodarone) or diltiazem/verapamil"}
• {"criterion_text":"- Resting heart rate <65 beats per minute on the day of surgery"}
• {"criterion_text":"- Systolic blood pressure <90 mmHg on the day of surgery"}
• {"criterion_text":"- Acute decompensated heart failure, cardiogenic shock, acute myocarditis"}
• {"criterion_text":"- Acute coronary syndrome within 2 months before surgery"}
• {"criterion_text":"- Stroke or transient cerebral ischaemia within 1 month before surgery"}
• {"criterion_text":"- Known severe liver or kidney disease (MDRD creatinine clearance <15 mL/min)"}

Primary endpoints

• {"endpoint_text":"- Myocardial injury after non-cardiac surgery (MINS) defined as any myocardial infarction and any elevated postoperative cardiac troponin judged as resulting from myocardial ischaemia during or within 30 days after noncardiac surgery","definition_or_measurement_approach":"Defined as any myocardial infarction and any elevated postoperative cardiac troponin judged as resulting from myocardial ischaemia during or within 30 days after noncardiac surgery."}

Secondary endpoints

• {"endpoint_text":"- Secondary outcomes at 30 days include: a composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest; vascular death; MINS not fulfilling the criteria of myocardial infarction; myocardial infarction; days alive and at home; stroke","definition_or_measurement_approach":"Measured at 30 days after surgery; includes composite and individual vascular outcomes as listed."}
• {"endpoint_text":"- health-related quality of life; cancellation/postponement of surgery on the day of surgery due to HR concerns; intraoperative mean arterial pressure; intraoperative heart rate; clinically important atrial fibrillation; safety outcomes including clinically significant bradycardia, clinically significant hypotension and phosphenes.","definition_or_measurement_approach":"Measured at 30 days (where specified) and perioperative/intraoperative monitoring for haemodynamic and safety outcomes as listed."}

Poland

Earliest CTIS Part Ii Submission Date

06-06-2024

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

524

Number Of Sites

25

Number Of Participants

2500

Primary sponsor

Full Name

Uniwersytet Jagiellonski Collegium Medicum

Organisation Type

Educational Institution

Country Of Registered Address

Poland