PeRiOperaTivE CardioproTection With Ivabradine in Non-cardiac Surgery

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-05

Study Completion Date

2022-01-11

Brief Summary

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Perioperative myocardial injury (PMI) after non-cardiac surgery (NCS), i.e. the elevation of postoperative troponin, occurs in nearly 20% of patients older than 45 years undergoing NCS and is independently and strongly associated with post-operative mortality (30-day mortality up to 10%). With over 300 million surgical interventions every year worldwide, PMI has a high clinical relevance on the health of the population.

Heart rate (HR) is an independent and modifiable risk factor for PMI and death after non-cardiac surgery. Numerous studies showed that beta-blockers decrease myocardial ischemia after surgery in a heart-rate dependent manner, but this beneficial effect is surpassed by an increased incidence of perioperative hypotension and death. Currently, no single intervention is available to decrease the risk of perioperative cardiac complications. Ivabradine (IVA) is a negative chronotropic agent without significant effects on contractility or vascular tone and has been shown to improve outcomes in the setting of chronic and acute heart diseases.

Rationale for pilot feasibility trial: the planned definitive large trial is a multicenter trial to investigate the efficacy of ivabradine to decrease perioperative myocardial injury. The intervention planned is complex and demands important resources. The investigators designed this pilot study to inform on the feasibility of the definitive large trial. This pilot study will also provide additional information that could help investigators improve the definitive large trial regarding recruitment, refinements to the study protocol and improving the participant's experience.

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Detailed Description

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Conditions

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Myocardial Injury Myocardial Ischemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Single center, randomized, placebo-controlled, double-blind, parallel group, feasibility pilot trial.

Patients will be randomized to receive ivabradine or placebo.

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ivabradine

Ivabradine will be administered in an individualized regimen adapted to the subject's heart rate at each visit in a dosage ranging from 0-7.5mg twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:

* If heart rate is ≥101 bpm: capsule D (Ivabradine 7.5 mg);
* If heart rate is 86-100 bpm: capsule C (Ivabradine 5 mg);
* If HR is 71-85 bpm: capsule B (Ivabradine 2.5 mg);
* If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (placebo).

Group Type EXPERIMENTAL

Ivabradine

Intervention Type DRUG

Ivabradine pills will be crushed and encapsulated for adequate dosing (0, 2.5mg, 5mg or 7.5 mg) and blinding.

Placebo

Intervention Type DRUG

Mannitol will be encapsulated for adequate blinding.

Placebo

Placebo will be administered twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:

* If heart rate is ≥101 bpm: capsule D (Placebo)
* If heart rate is 86-100 bpm: capsule C (Placebo)
* If HR is 71-85 bpm: capsule B (Placebo)
* If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (Placebo).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Mannitol will be encapsulated for adequate blinding.

Interventions

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Ivabradine

Ivabradine pills will be crushed and encapsulated for adequate dosing (0, 2.5mg, 5mg or 7.5 mg) and blinding.

Intervention Type DRUG

Placebo

Mannitol will be encapsulated for adequate blinding.

Intervention Type DRUG

Other Intervention Names

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Procoralan

Eligibility Criteria

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Inclusion Criteria

* Informed Consent as documented by signature of patient; AND
* Undergoing intermediate or high-risk non-cardiac surgery (as defined in European Society of Anaesthesiology guidelines) AND;
* One of the following:

o≥ 75 years old OR; o≥ 45 years old AND at least 1 risk factors independently associated with perioperative myocardial injury (history of coronary artery disease, chronic heart failure, peripheral artery disease, ischemic stroke, hypertension, diabetes mellitus, chronic kidney disease).

Exclusion Criteria

* Inability to provide informed consent;
* History of hypersensitivity or allergy to ivabradine;
* Emergency surgery (to be done within 24h of diagnosis);
* Shock or acute decompensated heart failure at trial inclusion;
* Low cardiac output syndrome;
* Arrhythmia:

* Atrial fibrillation or flutter;
* AV-block of 3rd degree;
* Sick sinus syndrome;
* Sino-atrial block;
* Pacemaker dependency;
* Unstable angina;
* Acute myocardial infarction in the 3 months preceding the trial;
* Stroke in the 3 months preceding the trial;
* Cirrhosis Child B and C;
* Renal failure with a Estimated Glomerular filtration rate ≤ 15 ml/min/1.73m2;
* Treatment with a strong cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin; josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone;
* Treatment with verapamil or diltiazem which are moderate CYP3A4 inhibitors and PGP inducers with heart rate reducing properties;
* Women who are pregnant or breast feeding;
* Childbearing potential (Of note, woman with history of hysterectomy, surgical sterilization or menopause for longer than 2 years are not considered with childbearing potential, independent of their age);
* Participation in another study with investigational drug within the 30 days preceding and during the present study;
* Previous enrolment into the current study.

Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No