Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

Study Overview
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Brief Summary
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Anthracyclines are associated with cardiotoxic effects. Previous studies suggest that enalapril, and or carvedilol, protect against cardiovascular effects of these drugs. Ivabradine selectively reduces heart rate through inhibition of the cardiac pace maker IF channel, thus prolonging the duration of spontaneous depolarization in the sinus node. Additionally, ivabradine might preserve myocardial perfusion without negative inotropic effect and probably maintain cardiac contractility despite the reduction of heart rate. Ivabradine has been shown to improve outcome in patients with heart failure and angina. The aim of this study is to evaluate whether ivabradine might prevent anthracycline-induced cardiotoxicity.

Official Title
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Ivabradine to Prevent Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial

Conditions
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Chemotherapy Effect, Neoplasms, Heart Failure, Cardiotoxicity, Oncology

Intervention / Treatment
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* Drug: Ivabradine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-year-old or older; Cancer diagnosis; Chemotherapy with anthracycline; Written informed consent Exclusion Criteria: Chronic Kidney Disease (Creatinine clearance inferior to 30mL/min/1.73m2) Bradycardia (heart rate less than 60 beats per minute) Atrial fibrilation; Previous diagnosis of heart failure; Pregnancy; History of previous hypersensibility to the study drug; Participating in another study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivabradine<br>Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session. | Drug: Ivabradine<br>* Ivabradine capsule<br>|
| Placebo Comparator: Placebo<br>Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session. | Drug: Placebo<br>* Placebo oral capsule.<br>* Other names: Placebo oral capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular function | Reduction in global longitudinal strain of at least 10% (GLS) | 365 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint of mortality or major cardiovascular outcomes | Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia) | 365 days after randomization | 
| Left ventricular dysfunction | Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%. | 365 days after randomization | 
| Incidence of myocardial injury | Levels of NT-proBNP and high-sensitivity cardiac troponin T | 90 days after randomization | 
| Incidence of myocardial injury | Levels of NT-proBNP and high-sensitivity cardiac troponin T | 180 days after randomization | 
| Incidence of myocardial injury | Levels of NT-proBNP and high-sensitivity cardiac troponin T | 365 days after randomization | 
| Diastolic dysfunction | Assessment by echocardiography the incidence of diastolic dysfunction using the following parameters: peak E-wave velocity, peak A-wave velocity, mitral valve (MV) E/A ratio, MV deceleration time, pulsed-wave tissue doppler imaging e' velocity, Mitral E/e', left atrium maximum volume index, pulmonary vein(PV) systole(S) wave, PV diastole (D) wave, continuous wave (CW) doppler: tricuspid regurgitation, systolic jet velocity; Color M- mode. | 365 days after randomization | 
| Ventricular function | Reduction in global longitudinal strain of at least 10% (GLS) | 180 days after randomization |