IPAC: Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

Sponsor

University of Sao Paulo (Other)

Overall Status

Unknown status

CT.gov ID

NCT03650205

Collaborator

(none)

160

Enrollment

Location

Arms

34.3

Anticipated Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms Heart Failure Cardiotoxicity Chemotherapy Effect Oncology	Drug: Ivabradine Drug: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jan 22, 2019

Anticipated Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ivabradine Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session.	Drug: Ivabradine Ivabradine capsule
Placebo Comparator: Placebo Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session.	Drug: Placebo Placebo oral capsule. Other Names: Placebo oral capsule

Arm

Intervention/Treatment

Active Comparator: Ivabradine

Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session.

Drug: Ivabradine

Ivabradine capsule

Placebo Comparator: Placebo

Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session.

Drug: Placebo

Placebo oral capsule.

Other Names:

Placebo oral capsule

Outcome Measures

Primary Outcome Measures

Ventricular function [365 days after randomization]
Reduction in global longitudinal strain of at least 10% (GLS)

Secondary Outcome Measures

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
Incidence of myocardial injury [180 days after randomization]
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Incidence of myocardial injury [365 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 Outcome Measures

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 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
Incidence of myocardial injury [180 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
Adverse events [365 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.
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
Left Ventricular Dimensions [yearly after randomization until 5 years]
LV diastolic diameter, LV diastolic diameter, LV diastolic diameter
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto do Cancer do Estado de Sao Paulo	Sao Paulo	SP	Brazil	01246000

Sponsors and Collaborators

University of Sao Paulo

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ludhmila Abrahão Hajjar, Clinical director of the Instituto do Coracao, Faculdade de Medicina, University of Sao Paulo

ClinicalTrials.gov Identifier:

NCT03650205

Other Study ID Numbers:

42559415520020065

First Posted:

Aug 28, 2018

Last Update Posted:

Apr 2, 2019

Last Verified:

Apr 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Cardiotoxicity

Study Results

No Results Posted as of Apr 2, 2019