Heart FailurePhase 2/3LENA-WP10NCT02654678
Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
A Phase 2/3 study testing Enalapril Orodispersible Minitablet in people with Heart Failure and Dilated Cardiomyopathy, run by Ethicare GmbH at 6 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 8 weeks to 12 years
- Conditions the study is for
- Heart Failure, Dilated Cardiomyopathy, Congenital Heart Disease
- What is being tested?
- Enalapril Orodispersible Minitablet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Mar 2016to Apr 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 weeks to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Netherlands2 sites
Sophia Children's Hospital Erasmus MC
Rotterdam, 3015 CN
Saskia N. de Wildt, MD,PhD, +31 10 7040704, s.dewildt@erasmusmc.nl
Tjitske van der Zanden, +31 10 7040704, t.vanderzanden@erasmusmc.nl
Wilhelmina Children's Hospital, University Medical Center Utrecht
Utrecht, 3584 CX
J.M.P. J. Breur, MD,PhD, + 31 8875 540 02, h.breur@umcutrecht.nl
J.M.P. J. Breur, MD,PhD
Austria1 site
Medical University of Vienna
Vienna, 1090
Christoph Male, Prof,MD,PhD, + 43 1 40400 32320, christoph.male@meduniwien.ac.at
Vanessa Swoboda, MD, + 43 1 40400 32320, v.swoboda@live.at
Hungary1 site
Hungarian Paediatric Heart Centre,Göttsegen Gyorgy Hungarian Institute of Cardiology
Budapest, 1095
András Szatmári, Prof,MD,PhD, +36 1 215 1220, szatmari@kardio.hu
Laszlo Ablonczy, MD, +36 1 215 1220, 'Laszlo Ablonczy' <ablonczyl@gmail.com>
Serbia1 site
Univerzitetska Dečja Klinika
Belgrade, 11129
Milica Bajcetic, Prof,MD,PhD, +38 1112060716, milica.bajcetic@udk.bg.ac.rs
Ida Jovanovic, Prof,MD,PhD, + 38 1112060716, idaj@rcub.bg.ac.rs
United Kingdom1 site
Great Ormond Street Hospital for Children NHS Trust
London, WC1N 3JH
Michael Burch, Prof,MD,PhD, +44 020 7405 9200, michael.burch@gosh.nhs.uk
Michael Burch, Prof,MD,PhD
About this study
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.
Read the 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.
- Being tested
- Enalapril Orodispersible Minitablet
- Medical subject headings
- Heart Failure, Cardiomyopathy, Dilated, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enalapril Orodispersible MinitabletDrug
Also called Enalapril ODMT
Weight-dependent long-term treatment scheme with enalapril ODMTs of 0.25 and/or 1 mg strength
| Study group | Role | What they receive |
|---|---|---|
| Enalapril Orodispersible Minitablets | Experimental | 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. Receives: Drug: Enalapril Orodispersible Minitablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Adverse Reactions
Adverse Reaction definition according to European Directive 2001/20/EC, assessed at each Visit concerning intensity and causality
Measured: up to month 10
Secondary outcomes (15)
Blood pressure
Measurement pre-dose after 5 minutes at rest at every Visit up to end of treatment at Month 10
Measured: At every Visit: (day 0, month 1, 4, 7, 10)
Renin
Renin to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Angiotensin 1
Angiotensin 1to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Aldosterone
Aldosterone to assess the Renin-angiotensin-aldosterone system (RAAS) measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
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
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Creatinine
Creatinine for renal monitoring measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Urea nitrogen
Urea nitrogen for renal monitoring measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Serum potassium
Serum potassium for renal monitoring measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Brain-Natriuretic-Peptides (BNP)
BNP measured at every visit up to end of treatment at Month 10 to observe disease severity
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Micro-albuminuria
Measurement of micro-albuminuria for renal monitoring measured at every Visit up to end of treatment at Month 10
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Clinical haematology
Assessment at First and Last Study Visit at the end of treatment at Month 10
Measured: Day 0 and Month 10
ECG
Assessment at First and Last Study Visit at the end of treatment at Month 10
Measured: Day 0 and Month 10
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
Measured: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
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
Measured: At each Visit: (day 0, month 1, 4, 7, 10)
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
Measured: At each Visit: (day 0, month 1, 4, 7, 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study startMar 2016
- Primary completionApr 2018 (estimated)
- Study completionApr 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ethicare GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Saskia N. de Wildt, MD,PhD, Study chair, Sophia Children's Hospital, Erasmus MCMichiel Dalinghaus, MD,PhD, Principal investigator, Sophia Children's Hospital, Erasmus MCJ.M.P. J. Breur, MD,PhD, Principal investigator, Wilhelmina Children's Hospital, University Medical Center UtrechtIda Jovanovic, Prof,MD,PhD, Principal investigator, Univerzitetska Dečja Klinika BelgradeChristoph Male, Prof,MD,PhD, Principal investigator, Medical University of ViennaMichael Burch, Prof,MD,PhD, Principal investigator, Great Ormond Street Hospital for Children NHS Trust LondonAndrás Szatmári, Prof,MD,PhD, Principal investigator, Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654678
- Sponsor's protocol ID
- 2015-602295-03
- Other IDs
- 2015-002397-21, 2015
- Acronym
- LENA-WP10
- Status last verified
- Jan 2016
- First submitted
- 4 Jan 2016
- Last updated
- 13 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Serious Adverse Event information
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
- ClinicalTrials.gov ID
- NCT02654678
- Acronym / sponsor ID
- LENA-WP10 / 2015-602295-03
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ethicare GmbHIndustry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Apr 2018 (estimated)
- Study completion
- Apr 2018 (estimated)
- First posted
- 13 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enalapril Orodispersible Minitablets | Experimental | Drug: Enalapril Orodispersible MinitabletIndividually 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. |
Who may qualify
- Ages
- 8 weeks to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enalapril Orodispersible MinitabletAlso: Enalapril ODMTWeight-dependent long-term treatment scheme with enalapril ODMTs of 0.25 and/or 1 mg strength | Drug | Enalapril Orodispersible Minitablets |
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
15 secondary outcomes
Blood pressure
Time frame: At every Visit: (day 0, month 1, 4, 7, 10)
Renin
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Angiotensin 1
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Aldosterone
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Plasma Renin Activity
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Creatinine
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Urea nitrogen
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Serum potassium
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Brain-Natriuretic-Peptides (BNP)
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Micro-albuminuria
Time frame: Pre-dose at each Visit: (day 0, month 1, 4, 7, 10)
Clinical haematology
Time frame: Day 0 and Month 10
ECG
Time frame: Day 0 and 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)
Acceptability assessment of enalapril ODMTs
Time frame: At each Visit: (day 0, month 1, 4, 7, 10)
Palatability assessment of enalapril ODMTs
Time frame: At each Visit: (day 0, month 1, 4, 7, 10)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2016.
- Individual participant dataSharing planned: Yes. Serious Adverse Event information
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saskia N. de Wildt, MD,PhD study chair
Sophia Children's Hospital, Erasmus MC
Michiel Dalinghaus, MD,PhD principal investigator
Sophia Children's Hospital, Erasmus MC
J.M.P. J. Breur, MD,PhD principal investigator
Wilhelmina Children's Hospital, University Medical Center Utrecht
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Enalapril Orodispersible Minitablet in people with Heart Failure and Dilated Cardiomyopathy, run by Ethicare GmbH at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands, Austria, Hungary, Serbia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephanie Laeer, Prof,MD,PhD (+49 211 8110740, Stephanie.Laeer@uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with Adverse Reactions (time frame: up to month 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2016.