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

ISRCTN	ISRCTN60567801
DOI	https://doi.org/10.1186/ISRCTN60567801
Secondary identifying numbers	CL2-16257-090

Submission date: 22/09/2011
Registration date: 10/11/2011
Last edited: 18/04/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration and not expected to be available in the future

Contact information

Prof Damien Bonnet
Scientific

Service de Cardiologie Pédiatrique
Hôpital Necker Enfants Malades
149 rue de Sèvres
Paris Cedex 15
75743
France

Study information

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
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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.
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
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

Eligibility

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 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 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

Institut de Recherches Internationales Servier (France)
Industry

50 rue Carnot
Suresnes
92284
France

Website	http://www.servier.com/
"ROR"	https://ror.org/034e7c066

Funders

Funder type

Industry

Institut de Recherches Internationales Servier (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Publication plan: Summary results are published in https://clinicaltrials.servier.com.
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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No

Editorial Notes

18/04/2018: Internal review.
28/03/2018: Publication and dissemination plan and IPD sharing statement updated.
24/01/2018: Publication plan and IPD sharing statement added.
29/11/2017: Results summary added.
18/01/2012: The overall trial end date was changed from 30/09/2012 to 30/09/2013.