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

Phase 3

Active, not recruiting

• Conditions: Myocardial Injury After Noncardiac Surgery (MINS); Myocardial Ischemia
• Interventions: Drug: Ivabradine; Drug: Placebo

• Registration Number: NCT05279651
• Lead Sponsor: Jagiellonian University

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.

Study Timeline

• Study First Submitted: 2022-03-04
• Study First Submitted QC: 2022-03-04
• Study First Posted: 2022-03-15
• Study Start: 2022-06-13
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-11
• Primary Completion: 2025-04-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 2146

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ivabradine	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
MINS	30 days after randomization	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.

Secondary Outcome Measures

Name	Time	Method
A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest	30 days after randomization	Number of patients who have at least one of the following: vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest
MINS not fulfilling the 4th universal definition of myocardial infarction	30 days after randomization	Number of patients who experience MINS not fulfilling the 4th universal definition of myocardial infarction
Myocardial infarction	30 days after randomization	Number of patients who experience a myocardial infarction
Vascular death	30 days after randomization	Number of patients who die of vascular cause
Stroke	30 days after randomization	Number of patients who experience a stroke
All-cause mortality	30 days after randomization	Number of patients who die of any cause
Days alive and at home	30 days after randomization	Average number of days when a patient is alive and out of hospital within 30 days after randomization
Health-related quality of life	30 days after randomization	Average health-related quality of life (based on EuroQol 5 Dimension, five-level version \[EQ-5D\])
Clinically important atrial fibrillation	30 days after randomization	Number of patients who experience clinically important atrial fibrillation
Clinically significant bradycardia	30 days after randomization	Number of patients who experience clinically significant bradycardia
Clinically significant hypotension	30 days after randomization	Number of patients who experience clinically significant hypotension
Phosphenes	30 days after randomization	Number of patients who experience phosphenes
Cancellation or postponement of surgery due to concerns about patient's heart rate	30 days after randomization	Number of surgeries cancelled or postponed due to heart rate concerns
Peak troponin concentration	30 days after randomization	Peak troponin concentration during the index hospitalization
Area under the curve troponin	30 days after randomization	Area under the curve of troponin concentrations measured during the hospitalization
Intraoperative mean arterial pressure	30 days after randomization	Intraoperative mean arterial pressure measured during the index surgery to calculate the average intraoperative mean arterial pressure
Intraoperative heart rate	30 days after randomization	Intraoperative heart rate measured during the index surgery to calculate the average heart rate

Trial Locations

Locations (26)

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; 🇵🇱 Gdańsk, Poland

Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny; 🇵🇱 Katowice, Poland

Szpital Specjalistyczny św. Łukasza w Końskich; 🇵🇱 Końskie, Poland

Szpital św. Rafała w Krakowie; 🇵🇱 Kraków, Poland

5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie; 🇵🇱 Kraków, Poland

Szpital Zakonu Bonifratrów św. Jana Grandego w Krakowie; 🇵🇱 Kraków, Poland

Krakowski Szpital Specjalistyczny im. Jana Pawła II; 🇵🇱 Kraków, Poland

SP ZOZ Szpital Uniwersytecki w Krakowie; 🇵🇱 Kraków, Poland

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie sp. z o.o.; 🇵🇱 Kraków, Poland

Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie; 🇵🇱 Kraków, 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; 🇵🇱 Warszawa, Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny; 🇵🇱 Warszawa, Poland

Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON; 🇵🇱 Warszawa, Poland

Uniwersytecki Szpital Kliniczny we Wrocławiu; 🇵🇱 Wrocław, 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

Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi; 🇵🇱 Łódź, Poland