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

Jagiellonian University

Status and phase: Enrolling; Phase 3

Conditions: Myocardial Ischemia; Myocardial Injury After Noncardiac Surgery (MINS)

Treatments: Drug: Ivabradine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05279651

PREVENT-MINS

Details and patient eligibility

About

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

Full description

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.

Enrollment: 2,500 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,500 participants in 2 patient groups, including a placebo group

Ivabradine

Active Comparator group

Description:

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.

Treatment:

Drug: Ivabradine

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo