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 |
| Protocol serial number | CL2-16257-090 |
| Sponsor | Institut de Recherches Internationales Servier (France) |
| Funder | Institut de Recherches Internationales Servier (France) |
- 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 of protocol
Not provided at time of registration and not expected to be available in the future
Contact information
Prof Damien Bonnet
Scientific
Scientific
Service de Cardiologie Pédiatrique
Hôpital Necker Enfants Malades
149 rue de Sèvres
Paris Cedex 15
75743
France
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised double-blind placebo-controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant 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 objectives | 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 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Ivabradine |
| Primary outcome measure(s) |
1. Characterization pharmacokinetics (PK) and PK/Pharmacodynamics (PD) at D014 and M000 |
| Key secondary outcome measure(s) |
1. Echocardiographic parameters over the study |
| Completion date | 30/09/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 90 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 15/10/2011 |
| Date of final enrolment | 30/09/2013 |
Locations
Countries of recruitment
- United Kingdom
- Australia
- Belgium
- Brazil
- Bulgaria
- Canada
- Denmark
- Finland
- France
- Germany
- Hungary
- India
- Italy
- Mexico
- Poland
- Portugal
- Romania
- Russian Federation
- Spain
- Sweden
Study participating centre
Service de Cardiologie Pédiatrique
Paris Cedex 15
75743
France
75743
France
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| 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 | |||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
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.
