Ivabradine to Prevent Anthracycline-induced Cardiotoxicity

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

The aim of this study is to investigate protective effects of ivabradine in adult cancer patients undergoing anthracycline-based chemotherapy.

Study Overview

• Status: Unknown
• Conditions: Patients With Cancer
• Intervention / Treatment: Drug: Ivabradine

Detailed Description

Cancer treatment with anthracyclines may cause heart damage and can lead to heart failure. There are drugs which may protect against cardiotoxic effects of anthracyclines (renin-angiotensin inhibitors and beta blockers), but they are not tolerated due to hypotension. Ivabradine is heart rate lowering drug without effect on blood pressure which was approved for treatment of angina pectoris and heart failure. The aim of this study is to investigate protective effects of ivabradine in cancer patients undergoing anthracycline-based chemotherapy.

Ivabradine selectively inhibits If currents in the sinus node and prolongs the duration of spontaneous depolarization. That controls the heart's contractions and regulates the heart rate. Additionally, ivabradine might preserve myocardial function and contractility without effect on blood pressure. Ivabradine was approved for symptomatic treatment of chronic stable angina pectoris and chronic heart failure.

The aim of this study is to investigate protective effects of ivabradine in adult cancer patients undergoing anthracycline-based chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sigita Aidietiene, MD, PhD; Phone Number: 37052365214; Email: sigita.aidietiene@santa.lt
• Study Contact Backup: Name: Egle Ciburiene, MD; Phone Number: 37052365214; Email: egle.ciburiene@santa.lt

Study Locations

• Lithuania
  • Vilnius, Lithuania, 08661
    • Recruiting
    • Vilnius University Hospital Santaros Klinikos
    • Contact: Egle Ciburiene, MD; Email: egle.ciburiene@santa.lt
    • Contact: Sigita Aidietiene, MD, PhD; Email: sigita.aidietiene@santa.lt
    • Principal Investigator: Sigita Aidietiene, MD, PHD
    • Sub-Investigator: Egle Ciburiene, MD
    • Sub-Investigator: Jelena Celutkiene, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• cancer patients undergoing anthracyclines based chemotherapy;
• heart rate (HR) > 70 times per minute;
• Written informed consent.

Exclusion Criteria:

• Contraindications for ivabradine administration;
• HR<70 times per minute;
• Incapability to complete informed consent;
• Severe valve disease;
• Left ventricular ejection fraction (LVEF)≤ 30 %;
• Other severe conditions;
• Poor echogenicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ivabradine; Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until the last chemotherapy session	Drug: Ivabradine; Ivabradine capsule
No Intervention: Usual care; Patient will receive usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left venticular dysfunction by global longitudinal strain (GLS).	Change in global longitudinal strain (GLS) at least by 3%.	1, 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of myocardial injury according to levels of high-sensitivity cardiac troponin T and NT-proBNP	Incidence of myocardial injury according to levels of high-sensitivity cardiac troponin T and NT-proBNP.	1, 3 and 6 months
Incidence of left ventricular systolic and diastolic dysfunction by 2D and 3D echocardiography.	Incidence of left ventricular (LV) dysfunction defined as drop of LV ejection fraction by ≥ 10%.	1, 3 and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of symptomatic heart failure.	Incidence of symptomatic heart failure.	1, 3 and 6 months
Changes in left ventricular and right ventricular dimensions by 2D and 3D echocardiography.	Changes in left ventricular and right ventricular dimensions by 2D and 3D echocardiography.	1, 3 and 6 months

Collaborators and Investigators

• Sponsor: Vilnius University
• Investigators: Principal Investigator: Sigita Aidietiene, MD, PhD, Vilnius University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: heart failure; cardiotoxicity; anthracycline chemotherapy
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiotoxicity
• Other Study ID Numbers: ICO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No