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

Primary Purpose

Acute Heart Failure, Dilated Cardiomyopathy

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Ivabradine 5Mg Tab
Sponsored by
Bambino Gesù Hospital and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Heart Failure focused on measuring Ivabradine, Heart Failure, Pediatric, Cardiomyopathy

Eligibility Criteria

6 Months - 17 Years (Child)All SexesDoes not accept 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.

Sites / Locations

  • Bambino Gesù Hospital and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ivabradine

Arm 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
May 26, 2020
Last Updated
December 4, 2020
Sponsor
Bambino Gesù Hospital and Research Institute
Collaborators
Ministero della Salute, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT04405804
Brief Title
Early Administration of Ivabradine in Children With Heart Failure
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 20, 2020 (Actual)
Primary Completion Date
January 2021 (Anticipated)
Study Completion Date
May 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bambino Gesù Hospital and Research Institute
Collaborators
Ministero della Salute, Italy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Heart Failure, Dilated Cardiomyopathy
Keywords
Ivabradine, Heart Failure, Pediatric, Cardiomyopathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Simon's two-stage design
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ivabradine
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Ivabradine 5Mg Tab
Intervention Description
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
Primary Outcome Measure Information:
Title
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
Description
To assess the response to ivabradine on heart rate after 14 days of stable therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary Outcome Measure Information:
Title
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up
Description
To assess the response to ivabradine on heart rate after 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance
Description
To assess the response to ivabradine on serum NT-proBNP levels after 14 days of stable therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up
Description
To assess the response to ivabradine on serum NT-proBNP levels after 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance
Description
To assess the correlation between heart rate and serum NT-proBNP levels after 14 days of stable therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up
Description
To assess the correlation between heart rate and serum NT-proBNP levels after 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
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
Description
To assess EF, Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular End Systolic Volume (LVESV) after 14 days of stable therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
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
Description
To assess EF, LVSV, LVDV after 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance
Description
To assess the response to ivabradine on systolic blood pressure after 14 days of stable therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up
Description
To assess the response to ivabradine on systolic blood pressure after 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)
Description
To assess the need to resort to inotropic drugs within 14 days of stable ivabradine therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)
Description
To assess the need to resort to inotropic drugs within 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
Number and % of dropouts at the end of maintenance
Description
To assess the frequency of patients who exit from the study within 14 days of stable ivabradine therapy
Time Frame
At the end of the two weeks maintenance period (17-29 days from enrollment)
Title
Number and % of dropouts at the end of follow-up
Description
To assess the frequency of patients who exit from the study within 16 weeks of follow-up
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Title
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
Description
To assess the period within main cardiological events would occur after the start of ivabradine therapy
Time Frame
At the end of the 16 weeks follow-up period (129-141 days from enrollment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachele Adorisio, MD
Organizational Affiliation
Bambino Gesù Hospital and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bambino Gesù Hospital and Research Institute
City
Rome
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Early Administration of Ivabradine in Children With Heart Failure

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