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Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril (LENA-WP10)

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ClinicalTrials.gov Identifier: NCT02654678
Recruitment Status : Unknown
Verified January 2016 by Ethicare GmbH.
Recruitment status was:  Not yet recruiting
First Posted : January 13, 2016
Last Update Posted : January 13, 2016
Sponsor:
Information provided by (Responsible Party):
Ethicare GmbH

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.

Condition or disease Intervention/treatment Phase
Heart Failure Dilated Cardiomyopathy Congenital Heart Disease Drug: Enalapril Orodispersible Minitablet Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
Study Start Date : March 2016
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018


Arm Intervention/treatment
Experimental: Enalapril Orodispersible Minitablets
Individually adapted dose of enalapril consisting of 1 to maximum 4 enalapril ODMTs of 0.25 mg and/or 1 mg and/or other prescribed treatment of heart failure.
Drug: Enalapril Orodispersible Minitablet
Weight-dependent long-term treatment scheme with enalapril ODMTs of 0.25 and/or 1 mg strength
Other Name: Enalapril ODMT




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Clinical haematology [ Time Frame: Day 0 and Month 10 ]
    Assessment at First and Last Study Visit at the end of treatment at Month 10

  12. ECG [ Time Frame: Day 0 and Month 10 ]
    Assessment at First and Last Study Visit at the end of treatment at Month 10

  13. 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

  14. 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

  15. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Weeks to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02654678


Contacts
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Contact: Stephanie Laeer, Prof,MD,PhD +49 211 8110740 Stephanie.Laeer@uni-duesseldorf.de
Contact: Ingrid Klingmann, MD,PhD +32 2 784 3693 iklingmann@pharmaplex.be

Locations
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Austria
Medical University of Vienna
Vienna, Austria, 1090
Contact: Christoph Male, Prof,MD,PhD    + 43 1 40400 32320    christoph.male@meduniwien.ac.at   
Contact: Vanessa Swoboda, MD    + 43 1 40400 32320    v.swoboda@live.at   
Principal Investigator: Christoph Male, Prof,MD,PhD         
Sub-Investigator: Vanessa Swoboda, MD         
Hungary
Hungarian Paediatric Heart Centre,Göttsegen Gyorgy Hungarian Institute of Cardiology
Budapest, Hungary, 1095
Contact: András Szatmári, Prof,MD,PhD    +36 1 215 1220    szatmari@kardio.hu   
Contact: Laszlo Ablonczy, MD    +36 1 215 1220    'Laszlo Ablonczy' <ablonczyl@gmail.com>   
Principal Investigator: András Szatmári, Prof,MD,PhD         
Sub-Investigator: Laszlo Ablonczy, MD         
Netherlands
Sophia Children's Hospital Erasmus MC
Rotterdam, Netherlands, 3015 CN
Contact: Saskia N. de Wildt, MD,PhD    +31 10 7040704    s.dewildt@erasmusmc.nl   
Contact: Tjitske van der Zanden    +31 10 7040704    t.vanderzanden@erasmusmc.nl   
Principal Investigator: Michiel Dalinghaus, MD,PhD         
Sub-Investigator: Marijke Van der Meulen, MD,PhD         
Wilhelmina Children's Hospital, University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Contact: J.M.P. J. Breur, MD,PhD    + 31 8875 540 02    h.breur@umcutrecht.nl   
Principal Investigator: J.M.P. J. Breur, MD,PhD         
Serbia
Univerzitetska Dečja Klinika
Belgrade, Serbia, 11129
Contact: Milica Bajcetic, Prof,MD,PhD    +38 1112060716    milica.bajcetic@udk.bg.ac.rs   
Contact: Ida Jovanovic, Prof,MD,PhD    + 38 1112060716    idaj@rcub.bg.ac.rs   
Principal Investigator: Ida Jovanovic, Prof,MD,PhD         
United Kingdom
Great Ormond Street Hospital for Children NHS Trust
London, United Kingdom, WC1N 3JH
Contact: Michael Burch, Prof,MD,PhD    +44 020 7405 9200    michael.burch@gosh.nhs.uk   
Principal Investigator: Michael Burch, Prof,MD,PhD         
Sponsors and Collaborators
Ethicare GmbH
Investigators
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Study Chair: Saskia N. de Wildt, MD,PhD Sophia Children's Hospital, Erasmus MC
Principal Investigator: Michiel Dalinghaus, MD,PhD Sophia Children's Hospital, Erasmus MC
Principal Investigator: J.M.P. J. Breur, MD,PhD Wilhelmina Children's Hospital, University Medical Center Utrecht
Principal Investigator: Ida Jovanovic, Prof,MD,PhD Univerzitetska Dečja Klinika Belgrade
Principal Investigator: Christoph Male, Prof,MD,PhD Medical University of Vienna
Principal Investigator: Michael Burch, Prof,MD,PhD Great Ormond Street Hospital for Children NHS Trust London
Principal Investigator: András Szatmári, Prof,MD,PhD Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology

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Responsible Party: Ethicare GmbH
ClinicalTrials.gov Identifier: NCT02654678    
Other Study ID Numbers: 2015-602295-03
2015-002397-21 ( EudraCT Number )
First Posted: January 13, 2016    Key Record Dates
Last Update Posted: January 13, 2016
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Serious Adverse Event information
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiomyopathies
Cardiomyopathy, Dilated
Cardiovascular Diseases
Cardiomegaly
Enalapril
Enalaprilat
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents