NCT03650205

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
160

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jan 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 13, 2018

Completed
15 days until next milestone

First Posted

Study publicly available on registry

August 28, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

January 22, 2019

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

April 2, 2019

Status Verified

April 1, 2019

Enrollment Period

2.7 years

First QC Date

August 13, 2018

Last Update Submit

April 1, 2019

Conditions

NeoplasmsHeart FailureCardiotoxicityChemotherapy EffectOncology

Outcome Measures

Primary Outcomes (1)

  • Ventricular function

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

    365 days after randomization

Secondary Outcomes (7)

  • Composite endpoint of mortality or major cardiovascular outcomes

    365 days after randomization

  • Left ventricular dysfunction

    365 days after randomization

  • Incidence of myocardial injury

    90 days after randomization

  • Incidence of myocardial injury

    180 days after randomization

  • Incidence of myocardial injury

    365 days after randomization

  • +2 more secondary outcomes

Other Outcomes (13)

  • Composite endpoint of mortality or major cardiovascular outcomes

    yearly after randomization until 5 years

  • Left ventricular dysfunction

    180 days after randomization

  • Incidence of myocardial injury

    90 days after randomization

  • +10 more other outcomes

Study Arms (2)

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.

Drug: Ivabradine

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.

Drug: Placebo

Interventions

IvabradineDRUG

Ivabradine capsule

Ivabradine
PlaceboDRUG

Placebo oral capsule.

Also known as: Placebo oral capsule
Placebo

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18-year-old or older;
  • Cancer diagnosis;
  • Chemotherapy with anthracycline;
  • Written informed consent

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, 01246000, Brazil

RECRUITING

Related Publications (1)

  • 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.

    PMID: 40357644DERIVED

MeSH Terms

Conditions

NeoplasmsHeart FailureCardiotoxicity

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and Injuries

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Central Study Contacts

Stephanie I Rizk, MD

CONTACT

+551138932000stephrizk@gmail.com

Ludhmila A Hajjar, MD, PhD

CONTACT

+551138932000ludhmila@terra.com.br

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical director of the Instituto do Coracao, Faculdade de Medicina

Study Record Dates

First Submitted

August 13, 2018

First Posted

August 28, 2018

Study Start

January 22, 2019

Primary Completion

October 1, 2021

Study Completion

December 1, 2021

Last Updated

April 2, 2019

Record last verified: 2019-04

Data Sharing

IPD Sharing
Will not share

Locations

BR(1)