Early Administration of Ivabradine in Children With Heart Failure (EASI-Child)

Bambino Gesù Hospital and Research Institute

Status and phase: Unknown; Phase 2

Conditions: Acute Heart Failure; Dilated Cardiomyopathy

Treatments: Drug: Ivabradine 5Mg Tab

Study type: Interventional

Funder types: Other

Identifiers

NCT04405804

2019-003902-29 (EudraCT Number)

1986 / 2019

Details and patient eligibility

About

This is a monocentric, prospective, single arm, not for profit study. It is designed to study the early use of ivabradine in patients with dilated cardiomyopathy and Ejection Fraction (EF) < 45%.

Full description

The study is divided into a screening and enrollment visit (V1) where eligibility for treatment will be confirmed. Ivabradine will be administered to eligible patients with increasing dosage during the titration period (TP) which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period (MP) of the drug for a further 14 days. The follow-up period (FU) will last 4 months.

The dose of ACE inhibitors will be introduced after 72 hours of clinical stability after the introduction of titrated ivabradine at maximum dose according to protocol. The anti-aldosterone will be introduced 24 hours after the introduction of ivabradine. The diuretic will not be modified during the titration phase of the drug, unless there is clinical necessity.

During the FU ivabradine will be continued at stable dosage, in order to maintain the target heart rate (HR) reached during the maintenance phase (HR > 80 bpm, in the group of patients older than 6-12 months, or HR > 70 bpm in patients aged 1-3 years or HR > 50 bpm between 3-18 years). In all patients, the drug dose will be decreased or discontinued in case of bradycardia (HR< 80 bpm in patients 6-12 months, HR< 70 bpm in patients 1-3 years of age or HR< 60 bpm in patients 3-18 years of age) and/or symptoms related to bradycardia or for other safety reasons.

Enrollment: 9 estimated patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Dilated cardiomyopathy defined according to the indications of the Cardiomyopathy Task Force (dilation > 2 Standard Deviations (SD) and hypokinesia);
• Class NYHA/Ross ≥ II;
• Ejection fraction < 40%;
• Patients with acute heart failure episodes (both new episode and relapse) in the last three months;
• Systolic blood pressure > 50° age and height;
• Heart rate: 6-12 months: ≥105 bpm, >1 year <3 years: ≥95 bpm, 3-5 years: ≥75 bpm, 5-18 years: >70 bpm.

Exclusion criteria

• Cardiogenic shock in the three months;
• Hypertrophic, restrictive or mixed cardiomyopathy;
• Acute lymphocytic myocarditis diagnosed with endomyocardial biopsy;
• Significant Valvular Pathology;
• Sinus block and congenital long QT syndrome;
• Atrial Fibrillation;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 2.5 times normal, bilirubin > 3 and creatinine > 2.5 mg/dL;
• Pregnancy and/or positive pregnancy test patients;
• Hypersensitivity to the active substance or any of the excipients;
• Participation in a clinical trial in which an experimental drug was administered within 30 days or 5 half-lives of the investigational drug;
• Chronic lung disease or other clinical condition that the investigating physician believes is incompatible with the study;
• eGFR <15 mL/min/1.73 m2.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

Ivabradine

Experimental group

Description:

Eligible patients will be given treatment with ivabradine during a titration period which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period of another 14 days. At the end of maintenance period, primary endpoint will be assessed. After maintenance period, the patient will continue ivabradine at the same dosage during a follow-up period that will last 4 months.

Treatment:

Drug: Ivabradine 5Mg Tab