Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril

Heart Failure Clinical Trial

— LENA-WP10  

Official title:

Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02654678
• Other study ID #: 2015-602295-03
• Secondary ID: 2015-002397-21
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• First received: January 4, 2016
• Last updated: January 12, 2016
• Start date: March 2016
• Est. completion date: April 2018

Study information

• Verified date: January 2016
• Source: Ethicare GmbH
• Contact: Stephanie Laeer, Prof,MD,PhD
• Phone: +49 211 8110740
• Email: Stephanie.Laeer[@]uni-duesseldorf.de
• Is FDA regulated: No
• Health authority: Austria: Austrian Medicines and Medical Devices AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Serbia: Medicines and Medical Devices AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyHungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial Summary

Paediatric long-term safety follow-up clinical trial in maximum 100 children with heart failure due to dilated cardiomyopathy or congenital heart disease, from 1 day to less than 12 years of age at recruitment into the preceding short-term pharmacokinetic (PK)/pharmacodynamic (PD) trials. Pharmacodynamic measurements and renal monitoring in all children after 1 , 4, 7 and 10 months of follow-up; in addition PK assessments as well as acceptability and palatability assessments in children still under enalapril Orodispersible Minitablet (ODMT) treatment.

Description:

This clinical trial is one of three clinical trials of the European Commission (FP7)-funded "LENA" (Labeling of Enalapril from Neonates to Adolescents) project: 50 children with heart failure due to dilated cardiomyopathy (LENA-Work Package (WP)08 Trial) and 50 children with heart failure due to congenital heart disease (LENA-WP09 Trial) get treated with an optimal dose of enalapril ODMTs for up to 8 weeks after thorough, individualised titration and get invited to join this 10 months Safety Follow-up Study (LENA-WP10 Trial).

Reliable data on the long-term safety of enalapril in paediatric patients are currently not available. By conducting this long-term Safety Follow-up Trial in children who received or still receive enalapril Orodispersible Minitablets at the end of the 8-weeks PK/PD LENA-Work Package (WP)08 (children with heart failure due to dilated cardiomyopathy) and LENA-WP09 (children with heart failure due to congenital heart disease) Trials using sensitive and highly specific assay methodology, it will be possible to add to the generation of reliable PK and PD data in the whole paediatric age range from birth to 12 years. In addition, this follow-up study will allow to systematically collect follow-up information over 10 more months, so in total 12 months, in paediatric patients under long-term enalapril ODMT treatment and in paediatric patients who had received at least 3 days of ODMT treatment but then stopped for any reason.

The End-of-study Visit of the WP08 and WP09 Trials is also the First Visit of the Follow-up Study. Further Visits occur after 1 month, 4 months, 7 months and 10 months.

At each Visit blood pressure and renal monitoring as well as pharmacodynamic parameters and adverse events are assessed. In children under ongoing enalapril ODMT treatment, single PK sampling as well as acceptability and palatability assessments are made at each Visit.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Weeks to 12 Years

Eligibility

Inclusion Criteria:

• Patients from the WP08 and WP09 Trials who have been treated with enalapril Orodispersible Minitablets and are still under ODMT treatment.

• Patients from the WP08 and WP09 Trials who have been treated for at least 3 days with enalapril Orodispersible Minitablets and are no longer under ODMT treatment.

• Written informed consent from parent(s)/legal representative provided written informed consent for participation in this long term follow-up study and assent from the patient according to national legislation and as far as achievable from the child.

Exclusion Criteria:

Patients who have been enrolled and treated in the WP08 or WP09 Trials have fulfilled the respective in- and exclusion criteria of those protocols. As it is the aim of this Follow-up Study to observe the safety of all patients exposed to enalapril ODMT treatment, no additional exclusion criteria are defined in this protocol. However, adapted to the health situation of the patient, the investigator will decide whether planned study activities can be performed.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Congenital Heart Disease
• Dilated Cardiomyopathy
• Heart Defects, Congenital
• Heart Failure

Intervention

Drug:
• Enalapril Orodispersible Minitablet
Weight-dependent long-term treatment scheme with enalapril ODMTs of 0.25 and/or 1 mg strength

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Hungary	Hungarian Paediatric Heart Centre,Göttsegen Gyorgy Hungarian Institute of Cardiology	Budapest
Netherlands	Sophia Children's Hospital Erasmus MC	Rotterdam
Netherlands	Wilhelmina Children's Hospital, University Medical Center Utrecht	Utrecht
Serbia	Univerzitetska Decja Klinika	Belgrade
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Ethicare GmbH

Countries where clinical trial is conducted

Austria,  Hungary,  Netherlands,  Serbia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with Adverse Reactions	Adverse Reaction definition according to European Directive 2001/20/EC, assessed at each Visit concerning intensity and causality	up to month 10	Yes
Secondary	Blood pressure	Measurement pre-dose after 5 minutes at rest at every Visit up to end of treatment at Month 10	At every Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Renin	Renin to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Angiotensin 1	Angiotensin 1to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Aldosterone	Aldosterone to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Plasma Renin Activity	Plasma renin activity to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Creatinine	Creatinine for renal monitoring measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Urea nitrogen	Urea nitrogen for renal monitoring measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Serum potassium	Serum potassium for renal monitoring measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Brain-Natriuretic-Peptides (BNP)	BNP measured at every visit up to end of treatment at Month 10 to observe disease severity	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Micro-albuminuria	Measurement of micro-albuminuria for renal monitoring measured at every Visit up to end of treatment at Month 10	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Clinical haematology	Assessment at First and Last Study Visit at the end of treatment at Month 10	Day 0 and Month 10	Yes
Secondary	ECG	Assessment at First and Last Study Visit at the end of treatment at Month 10	Day 0 and Month 10	Yes
Secondary	Plasma concentration of enalapril and its active metabolite enalaprilat under long-term treatment	At each Visit in children under enalapril ODMT treatment a single blood sample will be collected to measure the enalapril and enalaprilat plasma levels during long-term treatment; population-kinetic investigation	Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Acceptability assessment of enalapril ODMTs	Acceptability assessment at each Visit up to end of treatment at 10 months in children under enalapril ODMT treatment according to an age-appropriate scale	At each Visit: (day 0, month 1, 4, 7, 10)	Yes
Secondary	Palatability assessment of enalapril ODMTs	Palatability assessment at each Visit up to end of treatment at Month 10 in children under enalapril ODMT treatment according to an age-appropriate scale	At each Visit: (day 0, month 1, 4, 7, 10)	Yes

External Links

•   FP7-funded "LENA"-project, Grant Agreement 602295