Clinical trial NCT02654678: Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
Official title: Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Dilated Cardiomyopathy
Congenital Heart Disease
Lead sponsor: Ethicare GmbH
Sponsor class: INDUSTRY
First posted: 2016-01-13
Enrollment: 100
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with Adverse Reactions
timeFrame: up to month 10
Secondary outcomes:
measure: Blood pressure
timeFrame: At every Visit: (day 0, month 1, 4, 7, 10)
measure: Renin
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Angiotensin 1
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Aldosterone
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Plasma Renin Activity
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Creatinine
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Urea nitrogen
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Serum potassium
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Brain-Natriuretic-Peptides (BNP)
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Micro-albuminuria
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Clinical haematology
timeFrame: Day 0 and Month 10
measure: ECG
timeFrame: Day 0 and Month 10
measure: Plasma concentration of enalapril and its active metabolite enalaprilat under long-term treatment
timeFrame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
measure: Acceptability assessment of enalapril ODMTs
timeFrame: At each Visit: (day 0, month 1, 4, 7, 10)
measure: Palatability assessment of enalapril ODMTs
timeFrame: At each Visit: (day 0, month 1, 4, 7, 10)
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Budapest
country: Hungary
facility: Hungarian Paediatric Heart Centre,Göttsegen Gyorgy Hungarian Institute of Cardiology
city: Rotterdam
country: Netherlands
facility: Sophia Children's Hospital Erasmus MC
city: Utrecht
country: Netherlands
facility: Wilhelmina Children's Hospital, University Medical Center Utrecht
city: Belgrade
country: Serbia
facility: Univerzitetska Dečja Klinika
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
Study officials:
affiliation: Sophia Children's Hospital, Erasmus MC
name: Saskia N. de Wildt, MD,PhD
role: STUDY_CHAIR
affiliation: Sophia Children's Hospital, Erasmus MC
name: Michiel Dalinghaus, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wilhelmina Children's Hospital, University Medical Center Utrecht
name: J.M.P. J. Breur, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univerzitetska Dečja Klinika Belgrade
name: Ida Jovanovic, Prof,MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Vienna
name: Christoph Male, Prof,MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children NHS Trust London
name: Michael Burch, Prof,MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology
name: András Szatmári, Prof,MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: