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

• Register: ISRCTN
• Last refreshed on: 21 May 2018
• Main ID: ISRCTN60567801
• Date of registration: 10/11/2011
• Prospective Registration: No
• Primary sponsor: Institut de Recherches Internationales Servier (France)
• Public 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
• 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.
• Date of first enrolment: 15/10/2011
• Target sample size: 90
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN60567801
• Study type: Interventional
• Study design: Randomised double-blind placebo-controlled trial (Treatment)
• Phase: Phase II/III

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

Contacts

• Name: Damien Bonnet

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Paediatric dilated cardiomyopathy and symptomatic chronic heart failure
Circulatory System
Cardiomyopathy

Intervention(s)

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.

Primary Outcome(s)

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(s)

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

Secondary ID(s)

CL2-16257-090

Source(s) of Monetary Support

Institut de Recherches Internationales Servier (France)

Ethics review

Status:
Approval date:
Contact:

Ethics approval was obtained before recruitment of the first participants

Results

• Results available: Yes
• Date Completed: 30/09/2013