Myocardial Injury After Noncardiac Surgery (MINS), Myocardial Ischemia
Conditions
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
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.
Interventions
DRUGIvabradine
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.
DRUGPlacebo
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.
Sponsors
Population Health Research Institute
Vanderbilt University Medical Center
Jagiellonian University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Vascular death | 30 days after randomization | Number of patients who die of vascular cause |
| 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 |
| Clinically significant bradycardia | 30 days after randomization | Number of patients who experience clinically significant bradycardia |
Other
| Measure | Time frame | Description |
|---|---|---|
| Myocardial infarction | 1 year after randomization | Number of patients who experience a myocardial infarction |
| BIMS | 30 days after randomization | Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS) |
| Health-related quality of life | 1 year after randomization | Average health-related quality of life (based on EuroQol 5 Dimension, five-level version \[EQ-5D\]) |
| Stroke | 1 year after randomization | Number of patients who experience a stroke |
| Infection/Sepsis | 30 days after randomization | Number of patients who experience infection/sepsis |
| Cardiac revascularization | 30 days after randomization | Number of patients who undergo cardiac revascularization |
| Re-hospitalization for vascular reasons | 30 days after randomization | Number of patients re-hospitalized for vascular reasons |
| Acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction | 30 days after randomization | Number of patients who experience an acute myocardial injury according to Fourth Universal Definition of Myocardial Infarction |
| Non-fatal cardiac arrest | 30 days after randomization | Number of patients who experience non-fatal cardiac arrest |
| Acute congestive heart failure | 30 days after randomization | Number of patients who experience acute congestive heart failure |
| Any symptomatic or asymptomatic episode of deep vein thrombosis or pulmonary embolism | 30 days after randomization | Number of patients who experience any (symptomatic or asymptomatic) episode of deep vein thrombosis or pulmonary embolism |
| International Society on Thrombosis and Haemostasis (ISTH) major bleeding | 30 days after randomization | Number of patients who experience major bleeding (as defined by ISTH) |
| Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria | 30 days after randomization | Number of patients who experience an acute kidney injury (fulfilling KDIGO criteria) |
| Acute kidney injury requiring dialysis | 30 days after randomization | Number of patients who experience an acute kidney injury requiring dialysis |
| Amputation | 30 days after randomization | Number of patients who undergo an amputation |
| Days outside of intensive care unit | 30 days after randomization | Average number of days alive outside of intensive care/cardiac care unit within 30 days after randomization |
| Length of hospital stay | 30 days after randomization | Average length of hospital stay |
| Length of intensive care unit stay | 30 days after randomization | Average length of intensive care unit stay |
| Discharge destination from the hospital | 30 days after randomization | Number of patients discharge to home/long-term care facility/other |
| All-cause mortality | 1 year after randomization | Number of patients who die of any cause |
| Vascular death | 1 year after randomization | Number of patients who die of vascular cause |
Countries
Poland
Outcome results
None listed