Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2011-001292-39-GB
• Date of registration: 24/08/2011
• Prospective Registration: Yes
• Primary sponsor: Institut de Recherches Internationales Servier
• Public title: Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years.
• Scientific title: Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years. A randomised, double-blind, multicentre, placebo controlled, phase II/III dose-finding study with a PK/PD characterisation and a 1 year efficacy/safety evaluation.
• Date of first enrolment: 25/11/2011
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001292-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Bulgaria, Denmark, Finland, Germany, Hungary, Italy, Mexico, Portugal, Russian Federation, Spain, Sweden, United Kingdom

Contacts

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

Key inclusion & exclusion criteria

Inclusion criteria:
-Patients of both gender aged from 6 months to less than 18 years old
-Patients with dilated cardiomyopathy (DCM) receiving their usual treatment for chronic heart failure (CHF) at the optimal dose
-Patients in sinus rhythm
­Resting heart rate (HR) complying with the following criteria:
.HR >= 105 bpm in the age-subset [6-12[ months
.HR >= 95 bpm in the age-subset [1-3[ years
.HR >= 75 bpm in the age-subset [3-5[ years
.HR >= 70 bpm in the age-subset [5-18[ years.
-CHF class II to IV NYHA or Ross classification, stable for at leas 1 month prior to selection
Left ventricular (LV) dysfunction with LVEF <= 45% documented by echocardiography
LV dysfunction consecutive to idiopathic DCM, post-viral myocarditis DCM or ischaemic DCM, left ventricular non compaction with DCM as primary condition or post-anthracyclines DCM (provided the treatment by anthracyclines was stopped at least two years prior to the selection into the study)

Are the trial subjects under 18? yes
Number of subjects for this age range: 90
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Class I NYHA or Ross Classification (asymptomatic patients),
•History of symptomatic or sustained (= 30 sec) ventricular arrhythmia unless a cardioverter defibrillator was implanted,
•Patients with structural valvular disease or severe functional valvular disease requiring surgery,
•Significant systemic ventricular outflow obstruction,
•DCM secondary to muscular dystrophies, hemoglobinopathies, HIV, carnitine deficiency,
•Patients requiring unauthorised concomitant treatment
•Serum creatinine >2.0 mg/dL or >180 µmol/L (blood sample performed at ASSE visit),
•AST and/or ALT > 3 upper normal limits (blood sample performed at ASSE visit),
•Unstable cardiovascular condition at selection or inclusion.
•A girl having childbearing potential and sexually active not having contraception,


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paediatric dilated cardiomyopathy and symptomatic chronic heart failure
MedDRA version: 16.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: S16257-2
Product Code: S16527-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: PROCORALAN
Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 155974-008
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: PROCORALAN
Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Other descriptive name: SUB08357MIG
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 155974-00-8
Curre

Primary Outcome(s)

Main Objective: To determine the optimal dose of ivabradine to reach the target heart rate reduction (HRR) of 20% without inducing a bradycardia (i.e. HR should be greater than a predefined HR threshold by age subset) and/or signs or symptoms related to bradycardia,
­To assess the pharmacokinetic (PK) parameters of ivabradine and its active metabolite S 18982 after repeated oral administrations,
­To assess the PKPD relationship of ivabradine and its active metabolite S 18982 using heart rate as evaluation criterion.

Secondary Objective: ­To assess, compared to placebo, the effects of ivabradine at target dose, on:
.left ventricular ejection fraction, measured by echocardiography,
.clinical symptoms by using the NYHA/ROSS classification,
.global clinical status evaluated by the investigator/parents,
.cardiovascular biomarker by measuring NT-proBNP,
­To assess, compared to placebo, the long-term safety of ivabradine over 1-year.

Primary end point(s): -Characterization PK and PKPD
-Target HR achievement

Timepoint(s) of evaluation of this end point: PK measurements: at D014 and M000
Heart rate reduction (HRR): HR measurements during titration period (D000, D014, D028, D042, D056, M000)

Secondary Outcome(s)

Secondary end point(s): ­-Echocardiographic parameters
-­Heart failure symptoms severity
­-Cardiovascular biomarker NT- proBNP.
-Safety
-Quality of Life Questionnaire

Timepoint(s) of evaluation of this end point: over the study

Secondary ID(s)

2011-001292-39-FI

ISRCTN60567801

CL2-16257-090

Source(s) of Monetary Support

SRDL Servier Research and Development

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 31/07/2015
• Date Completed: 26/02/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001292-39/results