Condition category
Circulatory System
Date applied
22/09/2011
Date assigned
10/11/2011
Last edited
01/11/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Damien Bonnet

ORCID ID

Contact details

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

Additional identifiers

EudraCT 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

As of 18/01/2012, anticipated end date was modified from 30/09/2012 to 30/09/2013.

Ethics approval

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

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below 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

Phase

Phase II/III

Drug names

Ivabradine

Primary outcome measures

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 trial start date

15/10/2011

Overall trial end date

30/09/2013

Reason abandoned

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

Patient

Age group

Child

Gender

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

Trial 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

http://www.servier.com/

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

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes