Early Administration of Ivabradine in Children With Heart Failure

NCT04405804 | Unknown Phase 2 DMC

• 2 other identifiers: 1986 / 20192019-003902-29
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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%.

Conditions

Acute Heart Failure; Dilated Cardiomyopathy

Keywords

Ivabradine; Heart Failure; Pediatric; Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up

  At the end of the 16 weeks follow-up period (129-141 days from enrollment)

• Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance

  At the end of the two weeks maintenance period (17-29 days from enrollment)

• Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up

  At the end of the 16 weeks follow-up period (129-141 days from enrollment)

• Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance

  At the end of the two weeks maintenance period (17-29 days from enrollment)

• Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up

  At the end of the 16 weeks follow-up period (129-141 days from enrollment)

Study Arms (1)

Ivabradine

EXPERIMENTAL

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.

Drug: Ivabradine 5Mg Tab

Interventions

Ivabradine 5Mg Tab 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

Ivabradine

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead
• Ministero della Salute, Italy: collaborator

Study Sites (1)

Bambino Gesù Hospital and Research Institute

Rome, Italy

Location

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure; Cardiomyopathies

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rachele Adorisio, MD

  Bambino Gesù Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Simon's two-stage design

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: May 28, 2020
• Study Start: June 20, 2020
• Primary Completion: January 1, 2021
• Study Completion: May 1, 2021
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)