Cardiotoxicity, Chemotherapy Effect, Heart Failure, Neoplasms, Oncology
Conditions
Brief summary
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.
Interventions
DRUGIvabradine
Ivabradine capsule
DRUGPlacebo
Placebo oral capsule.
Sponsors
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventricular function | 365 days after randomization | Reduction in global longitudinal strain of at least 10% (GLS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint of mortality or major cardiovascular outcomes | 365 days after randomization | Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia) |
| Left ventricular dysfunction | 365 days after randomization | Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%. |
| Incidence of myocardial injury | 90 days after randomization | Levels of NT-proBNP and high-sensitivity cardiac troponin T |
| Diastolic dysfunction | 365 days after randomization | 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. |
| Ventricular function | 180 days after randomization | Reduction in global longitudinal strain of at least 10% (GLS) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Oxygen consumption (VO2) | 180 days after randomization | Measurement of VO2 by cardiopulmonary exercise test |
| Ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) | 180 days after randomization | Measurement of ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) by cardiopulmonary exercise test |
| Composite endpoint of mortality or major cardiovascular outcomes | yearly after randomization until 5 years | Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia) |
| Left ventricular geometry and mass | yearly after randomization until 5 years | LV mass, Septal thickness, Posterior wall thickness |
| Subgroup analyses regarding the primary outcome | 365 days after randomization | Type of cancer, gender, age |
| Left Ventricular Dimensions | yearly after randomization until 5 years | LV diastolic diameter, LV diastolic diameter, LV diastolic diameter |
| Left ventricular dysfunction | 180 days after randomization | Incidence of left ventricular (LV) dysfunction defined as reduction of LV |
| Incidence of myocardial injury | 90 days after randomization | Levels of NT-proBNP and high-sensitivity cardiac troponin T |
| Diastolic dysfunction | 180 days after randomization | 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. |
| Adverse events | 180 days after randomization | bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria |
| Heart rate variability | 180 days after randomization | Assessment of heart variability through 24-hour holter the following parameters: mRR - ms, SDNN - ms, SDANN - ms, SDNNi - ms, rMSSD-ms, NN50, pNN50. |
Countries
Brazil
Contacts
Primary ContactStephanie I Rizk, MD
Backup ContactLudhmila A Hajjar, MD, PhD
Outcome results
None listed