Ivabradine for Prevention of Myocardial Injury After Noncardiac Surgery Trial (PREVENT-MINS)

Phase 3Active Not RecruitingNCT05279651

Jagiellonian University2,146 enrolled

Overview

This study is a multicentre, randomized controlled trial of ivabradine versus placebo.

The PREVENT-MINS study is a 2,500 patient multicentre, superiority randomized controlled trial of ivabradine versus placebo. The primary objective of the trial is to determine the impact of ivabradine versus placebo on the risk of MINS in patients with or at risk of atherosclerotic disease who are followed for 30 days after noncardiac surgery.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,146

Conditions

Myocardial Injury After Noncardiac Surgery (MINS)Myocardial Ischemia

Interventions

IvabradineDRUG

Patients fulfilling haemodynamic requirements (i.e. systolic blood pressure ≥90 mmHg and sinus rhythm with a heart rate ≥65 beats per minute) will receive 5mg of oral ivabradine at least 1 hour before surgery and the first postoperative dose in the evening or in the morning after surgery, at least 12 hours after the preoperative dose. Starting on the day after surgery, patients will receive 5mg oral ivabradine twice a day and continue this treatment for 7 days after surgery or until hospital discharge.

PlaceboDRUG

Patients fulfilling haemodynamic requirements (i.e. systolic blood pressure ≥90 mmHg and sinus rhythm with a heart rate ≥65 beats per minute) will receive matching placebo at least 1 hour before surgery and the first postoperative dose in the evening or in the morning after surgery, at least 12 hours after the preoperative dose. Starting on the day after surgery, patients will receive matching placebo twice a day and continue this treatment for 7 days after surgery or until hospital discharge.

Eligibility

Sex: ALLMin age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Undergoing noncardiac surgery 2. ≥45 years of age 3. Expected to require at least an overnight hospital admission after surgery 4. Provide written informed consent to participate in the PREVENT-MINS Trial, AND 5. Fulfill ≥1 of the following 5 criteria (A-E): A. History of coronary artery disease B. History of peripheral arterial disease C. History of stroke D. Undergoing major vascular surgery, OR E. Any 3 of 9 risk criteria: i. Undergoing major surgery ii. History of congestive heart failure iii. History of a transient ischaemic attack iv. Diabetes and currently taking an oral hypoglycemic agent or insulin v. Age ≥70 years vi. History of hypertension vii. Serum creatinine \>175 µmol/L (\>2.0 mg/dl) viii. History of smoking within 2 years of surgery ix. Undergoing emergent/urgent surgery Exclusion Criteria: 1. 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 2. Transplanted heart (or on waiting list) 3. Use of a selected class I or III antiarrhythmic drug (quinidine, disopyramide, sotalol, ibutilide, amiodarone) or diltiazem/verapamil 4. Resting heart rate \<65 beats per minute on the day of surgery 5. Systolic blood pressure \<90 mmHg on the day of surgery 6. Acute decompensated heart failure, cardiogenic shock, acute myocarditis 7. Acute coronary syndrome within 2 months before surgery; 8. Stroke or transient cerebral ischaemia within 1 month before surgery 9. Known severe liver or kidney disease (MDRD creatinine clearance \<15 mL/min) 10. Inability to tolerate oral intake 11. Recent use of ivabradine (\<1 month) 12. Known allergy or hypersensitivity to ivabradine 13. Low-risk surgical procedure based on individual physician's judgment 14. Investigator considers the patient unreliable regarding requirement for study compliance 15. Women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding 16. Previously enrolled in the PREVENT-MINS study

Locations (26)

Outcomes

Primary Outcomes

MINS

Number of patients who experience 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.