Early Administration of Ivabradine in Children With Heart Failure

Acute Heart Failure Clinical Trial

— EASI-Child  

Official title:

A Monocentric, Open Label, Single Arm, Pilot Study on the Early Administration of Ivabradine in Children Aged >6 Months and <18 Years With Dilated Cardiomyopathy and Acute Heart Failure

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04405804
• Other study ID #: 1986 / 2019
• Secondary ID: 2019-003902-29
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: June 20, 2020
• Est. completion date: May 2021

Study information

• Verified date: December 2020
• Source: Bambino Gesù Hospital and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 9
• Est. completion date: May 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Heart Failure
• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy
• Heart Failure

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Italy	Bambino Gesù Hospital and Research Institute	Rome

Sponsors (2)

Lead Sponsor	Collaborator
Bambino Gesù Hospital and Research Institute	Ministero della Salute, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance	To assess the response to ivabradine on heart rate after 14 days of stable therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up	To assess the response to ivabradine on heart rate after 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance	To assess the response to ivabradine on serum NT-proBNP levels after 14 days of stable therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up	To assess the response to ivabradine on serum NT-proBNP levels after 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance	To assess the correlation between heart rate and serum NT-proBNP levels after 14 days of stable therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up	To assess the correlation between heart rate and serum NT-proBNP levels after 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of maintenance	To assess EF, Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular End Systolic Volume (LVESV) after 14 days of stable therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of follow-up	To assess EF, LVSV, LVDV after 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance	To assess the response to ivabradine on systolic blood pressure after 14 days of stable therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up	To assess the response to ivabradine on systolic blood pressure after 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)	To assess the need to resort to inotropic drugs within 14 days of stable ivabradine therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)	To assess the need to resort to inotropic drugs within 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Number and % of dropouts at the end of maintenance	To assess the frequency of patients who exit from the study within 14 days of stable ivabradine therapy	At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary	Number and % of dropouts at the end of follow-up	To assess the frequency of patients who exit from the study within 16 weeks of follow-up	At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Secondary	Time (days) from start of ivabradine therapy and new episode of acute heart failure, and/or implantation of mechanical assist device at the end of follow up	To assess the period within main cardiological events would occur after the start of ivabradine therapy	At the end of the 16 weeks follow-up period (129-141 days from enrollment)