Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

Heart Failure Clinical Trial

— IPAC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03650205
• Other study ID #: 42559415520020065
• Status: Recruiting
• Phase: N/A
• Start date: January 22, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: April 2019
• Source: University of Sao Paulo
• Contact: Stephanie I Rizk, MD
• Phone: +551138932000
• Email: stephrizk[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiotoxicity
• Chemotherapy Effect
• Heart Failure
• Neoplasms
• Oncology

Intervention

Drug:
• Ivabradine
Ivabradine capsule
• Placebo
Placebo oral capsule.

Locations

Country	Name	City	State
Brazil	Instituto do Cancer do Estado de Sao Paulo	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Left ventricular dysfunction	Incidence of left ventricular (LV) dysfunction defined as reduction of LV	180 days after randomization
Other	Incidence of myocardial injury	Levels of NT-proBNP and high-sensitivity cardiac troponin T	90 days after randomization
Other	Incidence of myocardial injury	Levels of NT-proBNP and high-sensitivity cardiac troponin T	180 days after randomization
Other	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
Other	Adverse events	bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria	180 days after randomization
Other	Adverse events	bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria	365 days after randomization
Other	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
Other	Oxygen consumption (VO2)	Measurement of VO2 by cardiopulmonary exercise test	180 days after randomization
Other	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
Other	Left Ventricular Dimensions	LV diastolic diameter, LV diastolic diameter, LV diastolic diameter	yearly after randomization until 5 years
Other	Left ventricular geometry and mass	LV mass, Septal thickness, Posterior wall thickness	yearly after randomization until 5 years
Other	Subgroup analyses regarding the primary outcome	Type of cancer, gender, age	365 days after randomization
Primary	Ventricular function	Reduction in global longitudinal strain of at least 10% (GLS)	365 days after randomization
Secondary	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
Secondary	Left ventricular dysfunction	Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%.	365 days after randomization
Secondary	Incidence of myocardial injury	Levels of NT-proBNP and high-sensitivity cardiac troponin T	90 days after randomization
Secondary	Incidence of myocardial injury	Levels of NT-proBNP and high-sensitivity cardiac troponin T	180 days after randomization
Secondary	Incidence of myocardial injury	Levels of NT-proBNP and high-sensitivity cardiac troponin T	365 days after randomization
Secondary	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
Secondary	Ventricular function	Reduction in global longitudinal strain of at least 10% (GLS)	180 days after randomization