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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivabradine | Active Comparator | Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session. |
|
| Placebo | Placebo Comparator | Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivabradine | Drug | Ivabradine capsule |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Ventricular function | Reduction in global longitudinal strain of at least 10% (GLS) | 365 days after randomization |
| 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 |
| 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) | yearly after randomization until 5 years |
| Left ventricular dysfunction |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stephanie I Rizk, MD | Contact | +551138932000 | 3271 | stephrizk@gmail.com |
| Ludhmila A Hajjar, MD, PhD | Contact | +551138932000 | 3272 | ludhmila@terra.com.br |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto do Cancer do Estado de Sao Paulo | Recruiting | São Paulo | São Paulo | 01246000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40357644 | Derived | Rizk SI, Costa IBSDS, Cruz CBBV, Pileggi B, de Almeida Andrade FT, Gonzalez TB, Bittar CS, Fukushima JT, Quintao VC, Osawa EA, Alves JBS, Fonseca SMR, Garcia DR, Pereira J, Buccheri V, Avila J, Kawahara LT, Barros CCS, Ikeoka LT, Nakada LN, Fellini M, Rocha VG, Rego EM, Hoff PMG, Filho RK, Landoni G, Hajjar LA. Randomized, Placebo-Controlled, Triple-Blind Clinical Trial of Ivabradine for the Prevention of Cardiac Dysfunction During Anthracycline-Based Cancer Therapy. J Am Heart Assoc. 2025 May 20;14(10):e039745. doi: 10.1161/JAHA.124.039745. Epub 2025 May 13. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D006333 | Heart Failure |
| D066126 | Cardiotoxicity |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077550 | Ivabradine |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Drug |
Placebo oral capsule. |
|
|
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 |
Incidence of left ventricular (LV) dysfunction defined as reduction of LV |
| 180 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 |
| 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. | 180 days after randomization |
| Adverse events | bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria | 180 days after randomization |
| Adverse events | bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria | 365 days after randomization |
| Heart rate variability | Assessment of heart variability through 24-hour holter the following parameters: mRR - ms, SDNN - ms, SDANN - ms, SDNNi - ms, rMSSD-ms, NN50, pNN50. | 180 days after randomization |
| Oxygen consumption (VO2) | Measurement of VO2 by cardiopulmonary exercise test | 180 days after randomization |
| Ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) | Measurement of ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) by cardiopulmonary exercise test | 180 days after randomization |
| Left Ventricular Dimensions | LV diastolic diameter, LV diastolic diameter, LV diastolic diameter | yearly after randomization until 5 years |
| Left ventricular geometry and mass | LV mass, Septal thickness, Posterior wall thickness | yearly after randomization until 5 years |
| Subgroup analyses regarding the primary outcome | Type of cancer, gender, age | 365 days after randomization |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |