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Ivabradine to Prevent Anthracycline-induced Cardiotoxicity (IPAC)

Primary Purpose

Neoplasms, Heart Failure, Cardiotoxicity

Status
Unknown status
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Ivabradine
Placebo
Sponsored by
University of Sao Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Neoplasms

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Instituto do Cancer do Estado de Sao PauloRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Ivabradine

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Ventricular function
Reduction in global longitudinal strain of at least 10% (GLS)

Secondary Outcome Measures

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

Full Information

First Posted
August 13, 2018
Last Updated
April 1, 2019
Sponsor
University of Sao Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT03650205
Brief Title
Ivabradine to Prevent Anthracycline-induced Cardiotoxicity
Acronym
IPAC
Official Title
Ivabradine to Prevent Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 22, 2019 (Actual)
Primary Completion Date
October 1, 2021 (Anticipated)
Study Completion Date
December 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Heart Failure, Cardiotoxicity, Chemotherapy Effect, Oncology

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ivabradine
Arm Type
Active Comparator
Arm Description
Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session.
Intervention Type
Drug
Intervention Name(s)
Ivabradine
Intervention Description
Ivabradine capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo oral capsule.
Primary Outcome Measure Information:
Title
Ventricular function
Description
Reduction in global longitudinal strain of at least 10% (GLS)
Time Frame
365 days after randomization
Secondary Outcome Measure Information:
Title
Composite endpoint of mortality or major cardiovascular outcomes
Description
Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia)
Time Frame
365 days after randomization
Title
Left ventricular dysfunction
Description
Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%.
Time Frame
365 days after randomization
Title
Incidence of myocardial injury
Description
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Time Frame
90 days after randomization
Title
Incidence of myocardial injury
Description
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Time Frame
180 days after randomization
Title
Incidence of myocardial injury
Description
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Time Frame
365 days after randomization
Title
Diastolic dysfunction
Description
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.
Time Frame
365 days after randomization
Title
Ventricular function
Description
Reduction in global longitudinal strain of at least 10% (GLS)
Time Frame
180 days after randomization
Other Pre-specified Outcome Measures:
Title
Composite endpoint of mortality or major cardiovascular outcomes
Description
Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia)
Time Frame
yearly after randomization until 5 years
Title
Left ventricular dysfunction
Description
Incidence of left ventricular (LV) dysfunction defined as reduction of LV
Time Frame
180 days after randomization
Title
Incidence of myocardial injury
Description
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Time Frame
90 days after randomization
Title
Incidence of myocardial injury
Description
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Time Frame
180 days after randomization
Title
Diastolic dysfunction
Description
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.
Time Frame
180 days after randomization
Title
Adverse events
Description
bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria
Time Frame
180 days after randomization
Title
Adverse events
Description
bradycardia, hypertension, atrial fibrillation, luminous phenomena, syncope, hypotension, erythema, rash, diplopia, vertigo, urticaria
Time Frame
365 days after randomization
Title
Heart rate variability
Description
Assessment of heart variability through 24-hour holter the following parameters: mRR - ms, SDNN - ms, SDANN - ms, SDNNi - ms, rMSSD-ms, NN50, pNN50.
Time Frame
180 days after randomization
Title
Oxygen consumption (VO2)
Description
Measurement of VO2 by cardiopulmonary exercise test
Time Frame
180 days after randomization
Title
Ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2)
Description
Measurement of ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) by cardiopulmonary exercise test
Time Frame
180 days after randomization
Title
Left Ventricular Dimensions
Description
LV diastolic diameter, LV diastolic diameter, LV diastolic diameter
Time Frame
yearly after randomization until 5 years
Title
Left ventricular geometry and mass
Description
LV mass, Septal thickness, Posterior wall thickness
Time Frame
yearly after randomization until 5 years
Title
Subgroup analyses regarding the primary outcome
Description
Type of cancer, gender, age
Time Frame
365 days after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie I Rizk, MD
Phone
+551138932000
Ext
3271
Email
stephrizk@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ludhmila A Hajjar, MD, PhD
Phone
+551138932000
Ext
3272
Email
ludhmila@terra.com.br
Facility Information:
Facility Name
Instituto do Cancer do Estado de Sao Paulo
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01246000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie I Rizk, MD
Phone
+551138933267
Email
stephrizk@gmail.com
First Name & Middle Initial & Last Name & Degree
Ludhmila A Hajar, MD, PhD
Phone
+551138933267
Email
ludhmila@terra.com.br

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

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