EArly adminiStration of Ivabradine in CHILDren with heart failure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale Pediatrico Bambino Gesu

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

19 Mar 2025 → ongoing

Decision date (initial)

2025-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ministero della Salute, Ricerca Corrente

External identifiers

EU CT number

2025-520916-32-00

EudraCT number

2019-003902-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the response to ivabradine administration in terms of a reduction in heart rate between 20 and 30% from baseline V1 to ivabradine administration on heart rate after 14 days of stable therapy (V3).

Secondary objectives 3

1. Evaluate the response to ivabradine administration in terms of heart rate reduction of 20 to 30% compared to baseline value V1 Evaluate the response to ivabradine administration on heart rate after 4 months of follow up (V4)
2. Evaluate the safety of ivabradine treatment in terms of: • systolic blood pressure; • symptomatic bradycardia; • adverse events deemed related to therapy
3. Evaluate the activity of ivabradine treatment in terms of: • • NT-Pro-BNP; • left ventricular function, calculated using 2D echocardiography (calculation of left ventricular volumes and ejection fraction)

Conditions and MedDRA coding

Acute hearth failure in dilated cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients ≥ 3 years of age and under 18 years of age and weight ≥ 25 kg; Dilated cardiomyopathy defined according to the indications of the Cardiomyopathy Task Force (dilation > 2 SD and hypokinesia); NYHA/Ross Classification ≥ II; Ejection fraction < 40%; Patients with episode of acute heart failure (both de novo and relapse) in the last three months; Systolic blood pressure > 50th percentile per age and height; Heart rate: 3-5 years ≥75 bpm; 5-18 years >70 bpm; Signed Informed Consent Form (ICF)/Assent by the subject

Exclusion criteria 2

1. Hypertrophic, restrictive or mixed cardiomyopathy; Acute lymphocytic myocarditis diagnosed by endomyocardial biopsy; Significant Valvular Pathology; Sinoatrial block and congenital long QT-syndrome; Atrial fibrillation; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 2.5 times above the normal values, bilirubin > 3mg/dL and creatinine > 2.5 mg/dL. Patients who are pregnant and/or have a positive pregnancy test • Hypersensitivity to the active substance or to any of the excipients. • Participation in a clinical study in which an experimental drug was administered within 30 days or 5 half-lives of the study drug.
2. Chronic lung disease or other clinical condition that, in the opinion of the investigator, is incompatible with the study.eGFR <15 mL/min/1.73 m2 Inability to swallow tablets.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of patients, both in absolute numbers and as a percentage, showing a clinical response to treatment, defined as the difference (reduction) expressed as a percentage between 20% and 30%, calculated between the baseline (V1) heart rate in bpm and that recorded after 14 days (V3) of stable therapy with ivabradine.

Secondary endpoints 5

1. Clinical response defined by the difference (reduction) expressed as a percentage, calculated between the heart rate value at baseline (V1) and at the end of the titration protocol (V2), and between the heart rate value recorded at the end of the stable therapy period with ivabradine after 4 months of follow-up (V4)
2. Difference from baseline (V1) in heart rate in bpm at the end of the titration period (V2), after 14 days (V3) of stable therapy with ivabradine. After 4 months of follow-up (V4)
3. Difference from baseline (V1) of serum NT-proBNP in pg/mL (mean (±SD)) at the end of the titration protocol (V2), after 14 days of stable therapy with ivabradine (V3), after 4 months of follow up (V4)
4. Correlation between heart rate and NT-proBNP value (Pearson test)
5. Difference from baseline (V1) in left ventricular function, calculated using 2D echocardiography (calculated left ventricular volumes and ejection fraction - mean (±SD), at the end of the titration protocol (V2), after 14 days of stable ivabradine therapy (V3), after 4 months of follow-up (V4)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale Pediatrico Bambino Gesu

Sponsor organisation

Ospedale Pediatrico Bambino Gesu

Address

Piazza Di Sant'onofrio 4

City

Rome

Postcode

00165

Country

Italy

Scientific contact point

Organisation

Ospedale Pediatrico Bambino Gesu

Contact name

Adorisio Rachele

Public contact point

Organisation

Ospedale Pediatrico Bambino Gesu

Contact name

Adorisio Rachele

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications