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

Myocardial Ischemia Clinical Trial

— PREVENT-MINS  

Official title:

Ivabradine for PREVENTion of Myocardial Injury After Noncardiac Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05279651
• Other study ID #: PREVENT-MINS
• Status: Recruiting
• Phase: Phase 3
• Start date: June 13, 2022
• Est. completion date: March 31, 2026

Study information

• Verified date: February 2024
• Source: Jagiellonian University
• Contact: Bozena Seczynska, PhD
• Phone: (+48) 124332847
• Email: bozena.seczynska[@]uj.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2500
• Est. completion date: March 31, 2026
• Est. primary completion date: March 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia
• Myocardial Injury After Noncardiac Surgery (MINS)
• Myocardial Ischemia
• Wounds and Injuries

Intervention

Drug:
• 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
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.

Locations

Country	Name	City	State
Poland	Szpital Uniwersytecki nr 1 im. dr Antoniego Jurasza w Bydgoszczy	Bydgoszcz
Poland	Specjalistyczny Szpital Wojewódzki w Ciechanowie	Ciechanów
Poland	ZZOZ Szpital Slaski w Cieszynie	Cieszyn
Poland	Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibinskiego Slaski Uniwersytet Medyczny	Katowice
Poland	Szpital Specjalistyczny sw. Lukasza w Konskich	Konskie
Poland	5 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Krakowie	Kraków
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla 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 Zeromskiego w Krakowie	Kraków
Poland	Szpital sw. Rafala w Krakowie	Kraków
Poland	Szpital Zakonu Bonifratrów sw. Jana Grandego w Krakowie	Kraków
Poland	Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Lódz
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 1 Pomorskiego Uniwersytetu Medycznego	Szczecin
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego	Szczecin
Poland	Specjalistyczny Szpital im. Edwarda Szczeklika w Tarnowie	Tarnów
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny	Warszawa
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciatka Jezus	Warszawa
Poland	Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON	Warszawa
Poland	Uniwersytecki Szpital Kliniczny we Wroclawiu	Wroclaw
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego w Katowicach	Zabrze
Poland	Szpital Uniwersytecki im. Karola Marcinkowskiego w Zielonej Górze	Zielona Góra

Sponsors (3)

Lead Sponsor	Collaborator
Jagiellonian University	Population Health Research Institute, Vanderbilt University Medical Center

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cardiac revascularization	Number of patients who undergo cardiac revascularization	30 days after randomization
Other	Re-hospitalization for vascular reasons	Number of patients re-hospitalized for vascular reasons	30 days after randomization
Other	Acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction	Number of patients who experience an acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction	30 days after randomization
Other	Non-fatal cardiac arrest	Number of patients who experience non-fatal cardiac arrest	30 days after randomization
Other	Acute congestive heart failure	Number of patients who experience acute congestive heart failure	30 days after randomization
Other	Any symptomatic or asymptomatic episode of deep vein thrombosis or pulmonary embolism	Number of patients who experience any (symptomatic or asymptomatic) episode of deep vein thrombosis or pulmonary embolism	30 days after randomization
Other	International Society on Thrombosis and Haemostasis (ISTH) major bleeding	Number of patients who experience major bleeding (as defined by ISTH)	30 days after randomization
Other	BIMS	Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)	30 days after randomization
Other	Infection/Sepsis	Number of patients who experience infection/sepsis	30 days after randomization
Other	Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria	Number of patients who experience an acute kidney injury (fulfilling KDIGO criteria)	30 days after randomization
Other	Acute kidney injury requiring dialysis	Number of patients who experience an acute kidney injury requiring dialysis	30 days after randomization
Other	Amputation	Number of patients who undergo an amputation	30 days after randomization
Other	Days outside of intensive care unit	Average number of days alive outside of intensive care/cardiac care unit within 30 days after randomization	30 days after randomization
Other	Length of hospital stay	Average length of hospital stay	30 days after randomization
Other	Length of intensive care unit stay	Average length of intensive care unit stay	30 days after randomization
Other	Discharge destination from the hospital	Number of patients discharge to home/long-term care facility/other	30 days after randomization
Other	All-cause mortality	Number of patients who die of any cause	1 year after randomization
Other	Vascular death	Number of patients who die of vascular cause	1 year after randomization
Other	Myocardial infarction	Number of patients who experience a myocardial infarction	1 year after randomization
Other	Cardiac revascularization	Number of patients who undergo cardiac revascularization	1 year after randomization
Other	Non-fatal cardiac arrest	Number of patients who experience non-fatal cardiac arrest	1 year after randomization
Other	Stroke	Number of patients who experience a stroke	1 year after randomization
Other	Health-related quality of life	Average health-related quality of life (based on EuroQol 5 Dimension, five-level version [EQ-5D])	1 year after randomization
Other	Amputation	Number of patients who have an amputation	1 year after randomization
Other	Re-hospitalization for vascular reasons	Number of patients who experience a re-hospitalization for vascular reasons	1 year after randomization
Primary	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.	30 days after randomization
Secondary	A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest	Number of patients who have at least one of the following: vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest	30 days after randomization
Secondary	MINS not fulfilling the 4th universal definition of myocardial infarction	Number of patients who experience MINS not fulfilling the 4th universal definition of myocardial infarction	30 days after randomization
Secondary	Myocardial infarction	Number of patients who experience a myocardial infarction	30 days after randomization
Secondary	Vascular death	Number of patients who die of vascular cause	30 days after randomization
Secondary	Stroke	Number of patients who experience a stroke	30 days after randomization
Secondary	All-cause mortality	Number of patients who die of any cause	30 days after randomization
Secondary	Days alive and at home	Average number of days when a patient is alive and out of hospital within 30 days after randomization	30 days after randomization
Secondary	Health-related quality of life	Average health-related quality of life (based on EuroQol 5 Dimension, five-level version [EQ-5D])	30 days after randomization
Secondary	Clinically important atrial fibrillation	Number of patients who experience clinically important atrial fibrillation	30 days after randomization
Secondary	Clinically significant bradycardia	Number of patients who experience clinically significant bradycardia	30 days after randomization
Secondary	Clinically significant hypotension	Number of patients who experience clinically significant hypotension	30 days after randomization
Secondary	Phosphenes	Number of patients who experience phosphenes	30 days after randomization
Secondary	Cancellation or postponement of surgery due to concerns about patient's heart rate	Number of surgeries cancelled or postponed due to heart rate concerns	30 days after randomization
Secondary	Peak troponin concentration	Peak troponin concentration during the index hospitalization	30 days after randomization
Secondary	Area under the curve troponin	Area under the curve of troponin concentrations measured during the hospitalization	30 days after randomization
Secondary	Intraoperative mean arterial pressure	Intraoperative mean arterial pressure measured during the index surgery to calculate the average intraoperative mean arterial pressure	30 days after randomization
Secondary	Intraoperative heart rate	Intraoperative heart rate measured during the index surgery to calculate the average heart rate	30 days after randomization