Early Administration of Ivabradine in Children With Heart Failure

NCT ID: NCT04405804

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-20
• Study Completion Date: 2021-05-31

Brief Summary

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%.

Detailed 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.

Conditions

Acute Heart Failure; Dilated Cardiomyopathy

Keywords

Ivabradine; Heart Failure; Pediatric; Cardiomyopathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ivabradine

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.

Group Type: EXPERIMENTAL

Ivabradine 5Mg Tab

Intervention Type: DRUG

Initial dose of ivabradine will be:

0.02 mg/kg/dose twice daily in patients between 6-12 months 0.05 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 2.5 mg/day in patients between 3-18 years with weight > 40 kg During titration phase, the dose may be increased, maintained, reduced or discontinued in accordance with titration rules. The titration rules will be adjusted on the basis of age subset and of each patient's evaluation during the titration phase, whether or not the target heart rate is reached (HR ≥ 20% compared to baseline HR) and whether or not are present bradycardia (HR should be greater than predefined by a HR threshold per age subset) and/or bradycardia-related symptoms.

Maximum dose to be reached will be:

0.2 mg/kg/dose twice daily in patients between 6-12 months 0.3 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 15 mg/day in patients between 3-18 years, weight > 40 kg

Interventions

Ivabradine 5Mg Tab

Initial dose of ivabradine will be:

0.02 mg/kg/dose twice daily in patients between 6-12 months 0.05 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 2.5 mg/day in patients between 3-18 years with weight > 40 kg During titration phase, the dose may be increased, maintained, reduced or discontinued in accordance with titration rules. The titration rules will be adjusted on the basis of age subset and of each patient's evaluation during the titration phase, whether or not the target heart rate is reached (HR ≥ 20% compared to baseline HR) and whether or not are present bradycardia (HR should be greater than predefined by a HR threshold per age subset) and/or bradycardia-related symptoms.

Maximum dose to be reached will be:

0.2 mg/kg/dose twice daily in patients between 6-12 months 0.3 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 15 mg/day in patients between 3-18 years, weight > 40 kg

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministero della Salute, Italy

OTHER

Sponsor Role: collaborator

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Rachele Adorisio

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rachele Adorisio, MD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Hospital and Research Institute

Locations

Bambino Gesù Hospital and Research Institute

Rome, , Italy

Countries

Italy

Other Identifiers

2019-003902-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1986 / 2019

Identifier Type: -

Identifier Source: org_study_id