Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
CL2-16257-090
Study information
Scientific title
Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure from ages 6 months to 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.
Acronym
Study hypothesis
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.
Ethics approval(s)
Ethics approval was obtained before recruitment of the first participants
Study design
Randomised double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Paediatric dilated cardiomyopathy and symptomatic chronic heart failure
Intervention
During the titration period:
[6-12] months: ivabradine, oral liquid paediatric formulation, the starting dose 0.02 mg/kg twice daily or placebo, then 4 titrations according to HR matching with placebo, i.e. 0.05 mg/kg, 0.10 mg/kg, 0.15 mg/kg and 0.20 mg/kg twice daily or placebo.
[1-3] and [3-18] years with weight < 40 kg: ivabradine, oral liquid paediatric formulation, at the starting dose 0.05 mg/kg twice daily or placebo, then 4 titrations according to HR matching with placebo, i.e. 0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg and 0.30 mg/kg twice daily or placebo.
[3-18] years with weight >= 40 kg: ivabradine adult tablet formulation, at the starting dose 2.5 mg twice daily or placebo, then 4 titrations according to HR matching with placebo, i.e. 5 mg, 7.5 mg, 10 mg and 15 mg twice daily or placebo.
During the maintenance period: ivabradine, oral liquid paediatric formulation (or adult tablet formulation), at the target dose, twice daily or placebo.
During 1 year treatment period: ivabradine, oral liquid paediatric formulation (or adult tablet formulation), at the dose defined during the maintenance period and adapted according to the weight at each visit, twice daily or placebo.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase II/III
Drug/device/biological/vaccine name(s)
Ivabradine
Primary outcome measure
1. Characterization pharmacokinetics (PK) and PK/Pharmacodynamics (PD) at D014 and M000
2. Target HR achievement: HR measurements during titration period (D000, D014, D028, D042, D056, M000)
Secondary outcome measures
1. Echocardiographic parameters over the study
2. Heart failure symptoms severity over the study
3. Cardiovascular biomarker NT- proBNP over the study
4. Safety over the study
Overall study start date
15/10/2011
Overall study end date
30/09/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients of both gender aged from 6 months to 18 years old
2. Patients with dilated cardiomyopathy (DCM) receiving their usual treatment for chronic heart failure (CHF) at the optimal dose
3. Patients in sinus rhythm
4. Resting heart rate (HR) complying with the following criteria:
4.1. HR >= 105 bpm in the age-subset [6-12] months
4.2. HR >= 95 bpm in the age-subset [1-3] years
4.3. HR >= 75 bpm in the age-subset [3-5] years
4.4. HR >= 70 bpm in the age-subset [5-18] years
5. CHF class II to IV NYHA or Ross classification, stable for at least 1 month prior to selection
6. Left ventricular (LV) dysfunction with left ventricular ejection fraction (LVEF) <= 45% documented by echocardiography LV dysfunction consecutive to idiopathic dilated cardiomyopathy (DCM), post-viral myocarditis DCM or ischaemic DCM
Participant type(s)
Patient
Age group
Child
Lower age limit
6 Months
Upper age limit
18 Years
Sex
Both
Target number of participants
90
Participant exclusion criteria
1. Class I NYHA or Ross Classification (asymptomatic patients)
2. Patients actively listed for transplantation at time of entry into the study or anticipated to undergo heart transplantation or corrective heartsurgery during the 1 year following entry into the study
3. History of symptomatic or sustained (≥ 30 sec) ventricular arrhythmiaunless a cardioverter defibrillator was implanted
4. Patients with structural valvular disease or severe functional valvulardisease requiring surgery
5. Significant systemic ventricular outflow obstruction
6. DCM secondary to muscular dystrophies, hemoglobinopathies, HIV,carnitine deficiency, anthracyclines
7. Patients requiring unauthorised concomitant treatment
8. Serum creatinine >2.0 mg/dL or >180 μmol/L (blood sampleperformed at ASSE visit)
9. AST and/or ALT > 3 upper normal limits (blood sample performed at ASSE visit)
10. Unstable cardiovascular condition at selection or inclusion
Recruitment start date
15/10/2011
Recruitment end date
30/09/2013
Locations
Countries of recruitment
Australia, Belgium, Brazil, Bulgaria, Canada, Denmark, Finland, France, Germany, Hungary, India, Italy, Mexico, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, United Kingdom
Study participating centre
Service de Cardiologie Pédiatrique
Paris Cedex 15
75743
France
Sponsor information
Organisation
Institut de Recherches Internationales Servier (France)
Sponsor details
50 rue Carnot
Suresnes
92284
France
Sponsor type
Industry
Website
ROR
Funders
Funder type
Industry
Funder name
Institut de Recherches Internationales Servier (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Publication plan:
Summary results are published in https://clinicaltrials.servier.com.
Intention to publish date
Individual participant data (IPD) sharing plan
The datasets generated during and/or analysed during the current study will be available upon request from https://clinicaltrials.servier.com if a Marketing Authorisation has been granted after 1st January 2014.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No |