Clinical trial NCT05279651: Ivabradine for Prevention of Myocardial Injury After Noncardiac Surgery Trial (PREVENT-MINS)
Official title: Ivabradine for PREVENTion of Myocardial Injury After Noncardiac Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myocardial Injury After Noncardiac Surgery (MINS)
Myocardial Ischemia
Keywords: Myocardial ischemia
Randomized controlled trial
Blinded
Noncardiac surgery
Cardiovascular events
Myocardial injury after non-cardiac surgery
Perioperative myocardial injury
Perioperative myocardial infarction
Perioperative medicine
Heart rate
Ivabradine
Cardiovascular Diseases
Troponin
Perioperative care
Physiological Effects of Drugs
Cardiovascular Agents
Cardiac Chronotropy
Heart Rate Control
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
name: Vanderbilt University Medical Center
First posted: 2022-03-15
Enrollment: 2146
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MINS
timeFrame: 30 days after randomization
Secondary outcomes:
measure: A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest
timeFrame: 30 days after randomization
measure: MINS not fulfilling the 4th universal definition of myocardial infarction
timeFrame: 30 days after randomization
measure: Myocardial infarction
timeFrame: 30 days after randomization
measure: Vascular death
timeFrame: 30 days after randomization
measure: Stroke
timeFrame: 30 days after randomization
measure: All-cause mortality
timeFrame: 30 days after randomization
measure: Days alive and at home
timeFrame: 30 days after randomization
measure: Health-related quality of life
timeFrame: 30 days after randomization
measure: Clinically important atrial fibrillation
timeFrame: 30 days after randomization
measure: Clinically significant bradycardia
timeFrame: 30 days after randomization
measure: Clinically significant hypotension
timeFrame: 30 days after randomization
measure: Phosphenes
timeFrame: 30 days after randomization
measure: Cancellation or postponement of surgery due to concerns about patient's heart rate
timeFrame: 30 days after randomization
measure: Peak troponin concentration
timeFrame: 30 days after randomization
measure: Area under the curve troponin
timeFrame: 30 days after randomization
measure: Intraoperative mean arterial pressure
timeFrame: 30 days after randomization
measure: Intraoperative heart rate
timeFrame: 30 days after randomization
Other outcomes:
measure: Cardiac revascularization
timeFrame: 30 days after randomization
measure: Re-hospitalization for vascular reasons
timeFrame: 30 days after randomization
measure: Acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction
timeFrame: 30 days after randomization
measure: Non-fatal cardiac arrest
timeFrame: 30 days after randomization
measure: Acute congestive heart failure
timeFrame: 30 days after randomization
measure: Any symptomatic or asymptomatic episode of deep vein thrombosis or pulmonary embolism
timeFrame: 30 days after randomization
measure: International Society on Thrombosis and Haemostasis (ISTH) major bleeding
timeFrame: 30 days after randomization
measure: BIMS
timeFrame: 30 days after randomization
measure: Infection/Sepsis
timeFrame: 30 days after randomization
measure: Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria
timeFrame: 30 days after randomization
measure: Acute kidney injury requiring dialysis
timeFrame: 30 days after randomization
measure: Amputation
timeFrame: 30 days after randomization
measure: Days outside of intensive care unit
timeFrame: 30 days after randomization
measure: Length of hospital stay
timeFrame: 30 days after randomization
measure: Length of intensive care unit stay
timeFrame: 30 days after randomization
measure: Discharge destination from the hospital
timeFrame: 30 days after randomization
measure: All-cause mortality
timeFrame: 1 year after randomization
measure: Vascular death
timeFrame: 1 year after randomization
measure: Myocardial infarction
timeFrame: 1 year after randomization
measure: Cardiac revascularization
timeFrame: 1 year after randomization
measure: Non-fatal cardiac arrest
timeFrame: 1 year after randomization
measure: Stroke
timeFrame: 1 year after randomization
measure: Health-related quality of life
timeFrame: 1 year after randomization
measure: Amputation
timeFrame: 1 year after randomization
measure: Re-hospitalization for vascular reasons
timeFrame: 1 year after randomization
Locations:
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. dr Antoniego Jurasza w Bydgoszczy
city: Ciechanów
country: Poland
facility: Specjalistyczny Szpital Wojewódzki w Ciechanowie
city: Cieszyn
country: Poland
facility: ZZOZ Szpital Śląski w Cieszynie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Gdańskiego Uniwersytetu Medycznego
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny
city: Końskie
country: Poland
facility: Szpital Specjalistyczny św. Łukasza w Końskich
city: Kraków
country: Poland
facility: Szpital św. Rafała w Krakowie
city: Kraków
country: Poland
facility: 5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie
city: Kraków
country: Poland
facility: Szpital Zakonu Bonifratrów św. Jana Grandego w Krakowie
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawła II
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie sp. z o.o.
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny 1 w Lublinie
city: Olsztyn
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Olsztynie
city: Opole
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Opolu
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 Pomorskiego Uniwersytetu Medycznego
city: Tarnów
country: Poland
facility: Specjalistyczny Szpital im. Edwarda Szczeklika w Tarnowie
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciątka Jezus
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny we Wrocławiu
city: Zabrze
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach
city: Zielona Góra
country: Poland
facility: Szpital Uniwersytecki im. Karola Marcinkowskiego w Zielonej Górze
city: Łódź
country: Poland
facility: Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
Study officials:
affiliation: Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College
name: Wojciech Szczeklik, Professor
role: PRINCIPAL_INVESTIGATOR
References: