Clinical trial NCT04405804: Early Administration of Ivabradine in Children With Heart Failure
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Heart Failure
Dilated Cardiomyopathy
Keywords: Ivabradine
Heart Failure
Pediatric
Cardiomyopathy
Lead sponsor: Bambino Gesù Hospital and Research Institute
Sponsor class: OTHER
Collaborators: name: Ministero della Salute, Italy
First posted: 2020-05-28
Enrollment: 9
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Simon's two-stage design
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary outcomes:
measure: Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: 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
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: 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
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: Number and % of dropouts at the end of maintenance
timeFrame: At the end of the two weeks maintenance period (17-29 days from enrollment)
measure: Number and % of dropouts at the end of follow-up
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
measure: 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
timeFrame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Bambino Gesù Hospital and Research Institute
Study officials:
affiliation: Bambino Gesù Hospital and Research Institute
name: Rachele Adorisio, MD
role: PRINCIPAL_INVESTIGATOR
References: