Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

Not Applicable

• Conditions: Neoplasms; Heart Failure; Cardiotoxicity; Chemotherapy Effect; Oncology
• Interventions: Drug: Placebo; Drug: Ivabradine

• Registration Number: NCT03650205
• Lead Sponsor: University of Sao Paulo

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-08-13
• Study First Submitted QC: 2018-08-26
• Study First Posted: 2018-08-28
• Study Start: 2019-01-22
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-01
• Last Update Posted: 2019-04-02
• Primary Completion: 2021-10-01
• Study Completion: 2021-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session.
Ivabradine	Ivabradine	Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session.

Primary Outcome Measures

Name	Time	Method
Ventricular function	365 days after randomization	Reduction in global longitudinal strain of at least 10% (GLS)

Secondary Outcome Measures

Name	Time	Method
Incidence of myocardial injury	365 days after randomization	Levels of NT-proBNP and high-sensitivity cardiac troponin T
Ventricular function	180 days after randomization	Reduction in global longitudinal strain of at least 10% (GLS)
Left ventricular dysfunction	365 days after randomization	Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%.
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)
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.

Trial Locations

Locations (1)

Instituto do Cancer do Estado de Sao Paulo; 🇧🇷 Sao Paulo, SP, Brazil