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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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 Summary:

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
Sponsor: Ethicare GmbH

Current Primary Outcome: Number of patients with Adverse Reactions [ Time Frame: up to month 10 ]

Adverse Reaction definition according to European Directive 2001/20/EC, assessed at each Visit concerning intensity and causality


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Blood pressure [ Time Frame: At every Visit: (day 0, month 1, 4, 7, 10) ]
    Measurement pre-dose after 5 minutes at rest at every Visit up to end of treatment at Month 10
  • Renin [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Renin to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
  • Angiotensin 1 [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Angiotensin 1to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
  • Aldosterone [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Aldosterone to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
  • Plasma Renin Activity [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Plasma renin activity to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
  • Creatinine [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Creatinine for renal monitoring measured at every Visit up to end of treatment at Month 10
  • Urea nitrogen [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Urea nitrogen for renal monitoring measured at every Visit up to end of treatment at Month 10
  • Serum potassium [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Serum potassium for renal monitoring measured at every Visit up to end of treatment at Month 10
  • Brain-Natriuretic-Peptides (BNP) [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    BNP measured at every visit up to end of treatment at Month 10 to observe disease severity
  • Micro-albuminuria [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    Measurement of micro-albuminuria for renal monitoring measured at every Visit up to end of treatment at Month 10
  • Clinical haematology [ Time Frame: Day 0 and Month 10 ]
    Assessment at First and Last Study Visit at the end of treatment at Month 10
  • ECG [ Time Frame: Day 0 and Month 10 ]
    Assessment at First and Last Study Visit at the end of treatment at Month 10
  • Plasma concentration of enalapril and its active metabolite enalaprilat under long-term treatment [ Time Frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10) ]
    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
  • Acceptability assessment of enalapril ODMTs [ Time Frame: At each Visit: (day 0, month 1, 4, 7, 10) ]
    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
  • Palatability assessment of enalapril ODMTs [ Time Frame: At each Visit: (day 0, month 1, 4, 7, 10) ]
    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


Original Secondary Outcome: Same as current

Information By: Ethicare GmbH

Dates:
Date Received: January 4, 2016
Date Started: March 2016
Date Completion: April 2018
Last Updated: January 12, 2016
Last Verified: January 2016