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

NCT ID: NCT05279651

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 2146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-13
• Study Completion Date: 2026-06-30

Brief Summary

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

Detailed 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.

Conditions

Myocardial Injury After Noncardiac Surgery (MINS); Myocardial Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ivabradine

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.

Group Type: ACTIVE_COMPARATOR

Ivabradine

Intervention Type: DRUG

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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Ivabradine

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Population Health Research Institute

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

Jagiellonian University

OTHER

Sponsor Role: lead

Responsible Party

Wojciech Szczeklik

Principal Investigator Wojciech Szczeklik MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wojciech Szczeklik, Professor

Role: PRINCIPAL_INVESTIGATOR

Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College

Locations

Szpital Uniwersytecki nr 1 im. dr Antoniego Jurasza w Bydgoszczy

Bydgoszcz, , Poland

Specjalistyczny Szpital Wojewódzki w Ciechanowie

Ciechanów, , Poland

ZZOZ Szpital Śląski w Cieszynie

Cieszyn, , Poland

Uniwersyteckie Centrum Kliniczne Gdańskiego Uniwersytetu Medycznego

Gdansk, , Poland

Szpital Specjalistyczny św. Łukasza w Końskich

Gmina Końskie, , Poland

Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny

Katowice, , Poland

Szpital św. Rafała w Krakowie

Krakow, , Poland

5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie

Krakow, , Poland

Szpital Zakonu Bonifratrów św. Jana Grandego w Krakowie

Krakow, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, , Poland

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie sp. z o.o.

Krakow, , Poland

Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie

Krakow, , Poland

Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi

Lodz, , Poland

Samodzielny Publiczny Szpital Kliniczny 1 w Lublinie

Lublin, , Poland

Wojewódzki Szpital Specjalistyczny w Olsztynie

Olsztyn, , Poland

Uniwersytecki Szpital Kliniczny w Opolu

Opole, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego

Szczecin, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 Pomorskiego Uniwersytetu Medycznego

Szczecin, , Poland

Specjalistyczny Szpital im. Edwarda Szczeklika w Tarnowie

Tarnów, , Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciątka Jezus

Warsaw, , Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny

Warsaw, , Poland

Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny we Wrocławiu

Wroclaw, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach

Zabrze, , Poland

Szpital Uniwersytecki im. Karola Marcinkowskiego w Zielonej Górze

Zielona Góra, , Poland

Countries

Poland

References

Szczeklik W, Fronczek J, Putowski Z, Wludarczyk A, Gorka J, Seczynska B, Gryszowka D, Widawska A, Bialka S, Palaczynski P, Borys M, Kutnik P, Czarnik T, Szczepanska A, Mozanski M, Mieszkowski M, Kotfis K, Trzebicki J, Sadowski L, Solek-Pastuszka J, Grudzien P, Mudyna W, Misiewska-Kaczur A, Owczuk R, Kudlinski B, Studzinska D, Pawlik J, Makowski A, Zietkiewicz M, Przydacz M, Gozdzik W, Gola W, Jasiewicz P, Zhao Z, Shyr Y, Devereaux PJ; PERI-CRIT Investigators. Ivabradine in Patients Undergoing Noncardiac Surgery: A Randomized Controlled Trial. Circulation. 2025 Oct 21;152(16):1126-1135. doi: 10.1161/CIRCULATIONAHA.125.076704. Epub 2025 Aug 30.

Reference Type: DERIVED

PMID: 40884771 (View on PubMed)

Other Identifiers

PREVENT-MINS

Identifier Type: -

Identifier Source: org_study_id