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

NCT05279651 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: PREVENT-MINS
• Study Type: interventional
• Target: 2,146
• Locations: 1 country
• Sites: 26

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest

  30 days after randomization

• MINS not fulfilling the 4th universal definition of myocardial infarction

  30 days after randomization

• Myocardial infarction

  30 days after randomization

• Vascular death

  30 days after randomization

• Stroke

  30 days after randomization

Other Outcomes (25)

• Cardiac revascularization

  30 days after randomization

• Re-hospitalization for vascular reasons

  30 days after randomization

• Acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction

  30 days after randomization

Study Arms (2)

Ivabradine

ACTIVE COMPARATOR

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.

Drug: Ivabradine

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Ivabradine 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.

Ivabradine

Placebo 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.

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing noncardiac surgery
• ≥45 years of age
• Expected to require at least an overnight hospital admission after surgery
• Provide written informed consent to participate in the PREVENT-MINS Trial, AND
• 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

You may not qualify if:

• 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
• Transplanted heart (or on waiting list)
• Use of a selected class I or III antiarrhythmic drug (quinidine, disopyramide, sotalol, ibutilide, amiodarone) or diltiazem/verapamil
• Resting heart rate \<65 beats per minute on the day of surgery
• Systolic blood pressure \<90 mmHg on the day of surgery
• Acute decompensated heart failure, cardiogenic shock, acute myocarditis
• Acute coronary syndrome within 2 months before surgery;
• Stroke or transient cerebral ischaemia within 1 month before surgery
• Known severe liver or kidney disease (MDRD creatinine clearance \<15 mL/min)
• Inability to tolerate oral intake
• Recent use of ivabradine (\<1 month)
• Known allergy or hypersensitivity to ivabradine
• Low-risk surgical procedure based on individual physician's judgment
• Investigator considers the patient unreliable regarding requirement for study compliance

Sponsors & Collaborators

• Jagiellonian University: lead
• Population Health Research Institute: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (26)

Szpital Uniwersytecki nr 1 im. dr Antoniego Jurasza w Bydgoszczy

Bydgoszcz, 85-094, Poland

Location

Specjalistyczny Szpital Wojewódzki w Ciechanowie

Ciechanów, 06-400, Poland

Location

ZZOZ Szpital Śląski w Cieszynie

Cieszyn, 43-400, Poland

Location

Uniwersyteckie Centrum Kliniczne Gdańskiego Uniwersytetu Medycznego

Gdansk, 80-952, Poland

Location

Szpital Specjalistyczny św. Łukasza w Końskich

Gmina Końskie, 26-200, Poland

Location

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

Katowice, 40-752, Poland

Location

Szpital św. Rafała w Krakowie

Krakow, 30-693, Poland

Location

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

Krakow, 30-901, Poland

Location

Szpital Zakonu Bonifratrów św. Jana Grandego w Krakowie

Krakow, 31-061, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, 31-202, Poland

Location

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, 31-501, Poland

Location

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

Krakow, 31-826, Poland

Location

Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie

Krakow, 31-913, Poland

Location

Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi

Lodz, 92-213, Poland

Location

Samodzielny Publiczny Szpital Kliniczny 1 w Lublinie

Lublin, 20-081, Poland

Location

Wojewódzki Szpital Specjalistyczny w Olsztynie

Olsztyn, 10-561, Poland

Location

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45-401, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego

Szczecin, 70-111, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 Pomorskiego Uniwersytetu Medycznego

Szczecin, 72-252, Poland

Location

Specjalistyczny Szpital im. Edwarda Szczeklika w Tarnowie

Tarnów, 33-100, Poland

Location

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciątka Jezus

Warsaw, 02-005, Poland

Location

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny

Warsaw, 02-097, Poland

Location

Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON

Warsaw, 04-141, Poland

Location

Uniwersytecki Szpital Kliniczny we Wrocławiu

Wroclaw, 50-556, Poland

Location

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

Zabrze, 41-800, Poland

Location

Szpital Uniwersytecki im. Karola Marcinkowskiego w Zielonej Górze

Zielona Góra, 65-001, Poland

Location

Related Publications (2)

• 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, Krolicki T, Szczepanska A, Hajder N, Mozanski M, Onichimowski D, 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. Ivabradine for prevention of myocardial injury after noncardiac surgery (PREVENT-MINS trial): study protocol for a randomized controlled trial. Trials. 2025 Nov 21;26(1):533. doi: 10.1186/s13063-025-09087-z.

  PMID: 41272750 DERIVED

• 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.

  PMID: 40884771 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia; Cardiovascular Diseases

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Heart Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Wojciech Szczeklik, Professor

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Wojciech Szczeklik MD PhD

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 15, 2022
• Study Start: June 13, 2022
• Primary Completion: April 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (26)