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

February 2, 2024 updated by: Wojciech Szczeklik, Jagiellonian University

Ivabradine for PREVENTion of Myocardial Injury After Noncardiac Surgery

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

2500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Poland
      • Bydgoszcz, Poland, 85-094
        • Not yet recruiting
        • Szpital Uniwersytecki nr 1 im. dr Antoniego Jurasza w Bydgoszczy
        • Contact:
        • Principal Investigator:
          • Przemysław Jasiewicz, MD PhD
      • Ciechanów, Poland, 06-400
        • Recruiting
        • Specjalistyczny Szpital Wojewódzki w Ciechanowie
        • Principal Investigator:
          • Jacek Milecki, MD
        • Contact:
      • Cieszyn, Poland, 43-400
        • Recruiting
        • ZZOZ Szpital Śląski w Cieszynie
        • Contact:
        • Principal Investigator:
          • Agnieszka Misiewska-Kaczur, MD, PhD
      • Katowice, Poland, 40-752
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny
        • Principal Investigator:
          • Anna Szczepańska, MD, PhD
        • Contact:
      • Końskie, Poland, 26-200
        • Recruiting
        • Szpital Specjalistyczny św. Łukasza w Końskich
        • Contact:
        • Principal Investigator:
          • Wojciech Gola, MD PhD
      • Kraków, Poland, 30-693
        • Recruiting
        • Szpital św. Rafała w Krakowie
        • Principal Investigator:
          • Jarosław Pawlik, MD,PhD
        • Contact:
      • Kraków, Poland, 30-901
        • Recruiting
        • 5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie
        • Contact:
        • Contact:
        • Principal Investigator:
          • Wojciech Szczeklik, MD, PhD
        • Sub-Investigator:
          • Jacek Górka, MD, PhD
      • Kraków, Poland, 31-061
        • Recruiting
        • Szpital Zakonu Bonifratrów św. Jana Grandego w Krakowie
        • Contact:
        • Principal Investigator:
          • Dorota Studzińska, MD, PhD
      • Kraków, Poland, 31-826
        • Recruiting
        • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie sp. z o.o.
        • Contact:
        • Principal Investigator:
          • Wojciech Mudyna, MD, PhD
      • Kraków, Poland, 31-202
        • Recruiting
        • Krakowski Szpital Specjalistyczny im. Jana Pawła II
        • Contact:
        • Principal Investigator:
          • Mirosław Ziętkiewicz, MD, PhD
      • Kraków, Poland, 31-501
        • Recruiting
        • SP ZOZ Szpital Uniwersytecki w Krakowie
        • Principal Investigator:
          • Mikołaj Przydacz, MD, PhD
        • Contact:
      • Kraków, Poland, 31-913
        • Recruiting
        • Szpital Specjalistyczny im. Stefana Żeromskiego w Krakowie
        • Contact:
        • Principal Investigator:
          • Paweł Jarocki, MD
      • Lublin, Poland, 20-081
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny 1 w Lublinie
        • Contact:
        • Principal Investigator:
          • Michał Borys, MD, PhD
      • Olsztyn, Poland, 10-561
        • Recruiting
        • Wojewodzki Szpital Specjalistyczny w Olsztynie
        • Contact:
        • Principal Investigator:
          • Dariusz Onichimowski, MD, PhD
      • Opole, Poland, 45-401
        • Recruiting
        • Uniwersytecki Szpital Kliniczny w Opolu
        • Contact:
        • Principal Investigator:
          • Tomasz Czarnik, MD, PhD
      • Szczecin, Poland, 72-252
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny Nr 1 Pomorskiego Uniwersytetu Medycznego
        • Contact:
        • Principal Investigator:
          • Joanna Sołek-Pastuszka, MD, PhD
      • Szczecin, Poland, 70-111
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego
        • Principal Investigator:
          • Katarzyna Kotfis, MD, PhD
        • Contact:
      • Tarnów, Poland, 33-100
        • Recruiting
        • Specjalistyczny Szpital im. Edwarda Szczeklika w Tarnowie
        • Contact:
        • Principal Investigator:
          • Paweł Grudzień, MD
      • Warszawa, Poland, 02-005
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciątka Jezus
        • Contact:
        • Principal Investigator:
          • Janusz Trzebicki, MD PhD
      • Warszawa, Poland, 04-141
        • Recruiting
        • Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON
        • Contact:
        • Principal Investigator:
          • Marcin Możański, MD, PhD
      • Warszawa, Poland, 02-097
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
        • Contact:
        • Principal Investigator:
          • Adam Makowski, MD
      • Wrocław, Poland, 50-556
        • Recruiting
        • Uniwersytecki Szpital Kliniczny we Wrocławiu
        • Contact:
        • Principal Investigator:
          • Waldemar Goździk, MD, PhD
      • Zabrze, Poland, 41-800
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach
        • Contact:
        • Principal Investigator:
          • Szymon Białka, MD, PhD
      • Zielona Góra, Poland, 65-001
        • Recruiting
        • Szpital Uniwersytecki im. Karola Marcinkowskiego w Zielonej Górze
        • Contact:
        • Principal Investigator:
          • Bartosz Kudliński, MD, PhD
      • Łódź, Poland, 92-213
        • Recruiting
        • Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
        • Contact:
          • Centralny Szpital Kliniczny Uniwersytetu Medycznego Łódź
          • Email: ckd@csk.umed.pl
        • Principal Investigator:
          • Waldemar Machała, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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 Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MINS
Time Frame: 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.
30 days after randomization

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
BIMS
Time Frame: 30 days after randomization
Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)
30 days after randomization
Length of hospital stay
Time Frame: 30 days after randomization
Average length of hospital stay
30 days after randomization
All-cause mortality
Time Frame: 1 year after randomization
Number of patients who die of any cause
1 year after randomization
Myocardial infarction
Time Frame: 1 year after randomization
Number of patients who experience a myocardial infarction
1 year after randomization
Cardiac revascularization
Time Frame: 30 days after randomization
Number of patients who undergo cardiac revascularization
30 days after randomization
Re-hospitalization for vascular reasons
Time Frame: 30 days after randomization
Number of patients re-hospitalized for vascular reasons
30 days after randomization
Acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction
Time Frame: 30 days after randomization
Number of patients who experience an acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction
30 days after randomization
Non-fatal cardiac arrest
Time Frame: 30 days after randomization
Number of patients who experience non-fatal cardiac arrest
30 days after randomization
Acute congestive heart failure
Time Frame: 30 days after randomization
Number of patients who experience acute congestive heart failure
30 days after randomization
Any symptomatic or asymptomatic episode of deep vein thrombosis or pulmonary embolism
Time Frame: 30 days after randomization
Number of patients who experience any (symptomatic or asymptomatic) episode of deep vein thrombosis or pulmonary embolism
30 days after randomization
International Society on Thrombosis and Haemostasis (ISTH) major bleeding
Time Frame: 30 days after randomization
Number of patients who experience major bleeding (as defined by ISTH)
30 days after randomization
Infection/Sepsis
Time Frame: 30 days after randomization
Number of patients who experience infection/sepsis
30 days after randomization
Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria
Time Frame: 30 days after randomization
Number of patients who experience an acute kidney injury (fulfilling KDIGO criteria)
30 days after randomization
Acute kidney injury requiring dialysis
Time Frame: 30 days after randomization
Number of patients who experience an acute kidney injury requiring dialysis
30 days after randomization
Amputation
Time Frame: 30 days after randomization
Number of patients who undergo an amputation
30 days after randomization
Days outside of intensive care unit
Time Frame: 30 days after randomization
Average number of days alive outside of intensive care/cardiac care unit within 30 days after randomization
30 days after randomization
Length of intensive care unit stay
Time Frame: 30 days after randomization
Average length of intensive care unit stay
30 days after randomization
Discharge destination from the hospital
Time Frame: 30 days after randomization
Number of patients discharge to home/long-term care facility/other
30 days after randomization
Vascular death
Time Frame: 1 year after randomization
Number of patients who die of vascular cause
1 year after randomization
Cardiac revascularization
Time Frame: 1 year after randomization
Number of patients who undergo cardiac revascularization
1 year after randomization
Non-fatal cardiac arrest
Time Frame: 1 year after randomization
Number of patients who experience non-fatal cardiac arrest
1 year after randomization
Stroke
Time Frame: 1 year after randomization
Number of patients who experience a stroke
1 year after randomization
Health-related quality of life
Time Frame: 1 year after randomization
Average health-related quality of life (based on EuroQol 5 Dimension, five-level version [EQ-5D])
1 year after randomization
Amputation
Time Frame: 1 year after randomization
Number of patients who have an amputation
1 year after randomization
Re-hospitalization for vascular reasons
Time Frame: 1 year after randomization
Number of patients who experience a re-hospitalization for vascular reasons
1 year after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jagiellonian University

Collaborators

Vanderbilt University Medical Center
Population Health Research Institute

Investigators

  • Principal Investigator: Wojciech Szczeklik, Professor, Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2022

Primary Completion (Estimated)

March 15, 2025

Study Completion (Estimated)

March 31, 2026

Study Registration Dates

First Submitted

March 4, 2022

First Submitted That Met QC Criteria

March 4, 2022

First Posted (Actual)

March 15, 2022

Study Record Updates

Last Update Posted (Estimated)

February 5, 2024

Last Update Submitted That Met QC Criteria

February 2, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREVENT-MINS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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