Ivabradine for PREVENTion of Myocardial Injury after Noncardiac Surgery (MINS) - PREVENT-MINS Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uniwersytet Jagiellonski Collegium Medicum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

2 Jun 2022 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515226-81-00

EudraCT number

2020-004877-38

ClinicalTrials.gov

NCT05279651

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the effect of perioperative administration of ivabradine in patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery. The primary outcome is 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 objectives 1

1. To determine the impact of ivabradine on the following outcomes at 30 days after surgery: a composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest; vascular death; MINS not fulfilling the criteria of myocardial infarction; myocardial infarction; peri-operative myocardial infraction/injury; days alive and at home; stroke; all-cause mortality; health-related quality of life; cancellation/postponement of surgery on the day of surgery due to HR concerns; cancellation/postponement of surgery on the day of surgery due to troponin elevation concerns; intraoperative mean arterial pressure; intraoperative heart rate; clinically important atrial fibrillation; safety outcomes including clinically significant bradycardia, clinically significant hypotension and phosphenes.

Conditions and MedDRA coding

Myocardial Injury after Noncardiac Surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Undergoing noncardiac surgery
2. ≥45 years of age
3. Expected to require at least an overnight hospital stay after surgery
4. Written informed consent to participate in the PREVENT-MINS Trial provided
5. Fulfil ≥1 of the following 5 criteria (A-E): A. Current or prior history of coronary artery disease as defined by any one of the following 7 criteria: i. History of angina; ii. History of acute coronary syndrome; iii. History of a segmental cardiac wall motion abnormality on echocardiography or a segmental fixed defect on radionuclide imaging; iv. History of a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test demonstrating cardiac ischaemia; v. History of a coronary angiographic or CT coronary angiographic evidence of atherosclerotic stenosis ≥50% of the diameter of any coronary artery; vi. ECG with pathological Q waves in at least two contiguous leads; OR vii. Previous coronary artery revascularization, (i.e. percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]);
6. Fulfil ≥1 of the following 5 criteria (A-E): B. Peripheral arterial disease as defined by a physician diagnosis of a current, or prior history of any of the following 4 criteria: i. Intermittent claudication; ii. Vascular surgery OR percutaneous transluminal angioplasty (PTA) for atherosclerotic disease; iii. An ankle/brachial systolic blood pressure ratio <0.90 in either leg at rest; OR iv. Angiographic, CT angiographic or doppler findings demonstrating >70% stenosis in a noncardiac artery;
7. Fulfil ≥1 of the following 5 criteria (A-E): C. History of stroke as defined by any one of the following 2 criteria: i. A physician diagnosis of stroke; OR ii. CT or MRI evidence of a prior stroke;
8. Fulfil ≥1 of the following 5 criteria (A-E): D. Undergoing major vascular surgery defined as all vascular surgeries (including any above foot amputation) with the exception of arteriovenous shunt, vein stripping procedures (varicose vein surgery), carotid endarterectomies, endovascular abdominal aortic aneurysm repair (EVAR); OR
9. Fulfil ≥1 of the following 5 criteria (A-E): E. Any 3 of 9 risk criteria: i. Undergoing major surgery defined as: intraperitoneal, intrathoracic, retroperitoneal, or major orthopaedic; ii. History of congestive heart failure defined as a physician diagnosis of a current or prior episode of congestive heart failure OR prior radiographic evidence of vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary oedema; iii. History of a transient ischaemic attack; iv. Diabetes diagnosis and currently taking hypoglycemic agent; v. Age ≥70 years; vi. History of hypertension; vii. Serum creatinine >175 μmol/L (>2.0 mg/dl) based on the most recent values before randomisation; viii. History of smoking within 2 years of surgery; and ix. Undergoing emergent/urgent surgery, defined as surgery that a surgeon schedules to go to the operating room within 48 hours from an acute presentation to the hospital.

Exclusion criteria 16

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 trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 2

1. Secondary outcomes at 30 days include: a composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest; vascular death; MINS not fulfilling the criteria of myocardial infarction; myocardial infarction; days alive and at home; stroke
2. health-related quality of life; cancellation/postponement of surgery on the day of surgery due to HR concerns; intraoperative mean arterial pressure; intraoperative heart rate; clinically important atrial fibrillation; safety outcomes including clinically significant bradycardia, clinically significant hypotension and phosphenes.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uniwersytet Jagiellonski Collegium Medicum

Sponsor organisation

Uniwersytet Jagiellonski Collegium Medicum

Address

Ul. Sw. Anny 12

City

Cracow

Postcode

31-008

Country

Poland

Scientific contact point

Organisation

Uniwersytet Jagiellonski Collegium Medicum

Contact name

prof. dr hab. Wojciech Szczeklik

Public contact point

Organisation

Uniwersytet Jagiellonski Collegium Medicum

Contact name

prof. dr hab. Marek Sanak

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications