Orodispersible Minitablets of Enalapril in Young Children With Heart Failure Due to Congenital Heart Disease

NCT ID: NCT02652741

Last Updated: 2016-01-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-06-30

Brief Summary

Paediatric clinical trial in 50 children, from newborn to less than 6 years of age, suffering from heart failure due to congenital heart disease, to obtain paediatric pharmacokinetic and pharmacodynamic data of enalapril and its active metabolite enalaprilat while treated for 8 weeks with enalapril in form of Orodispersible Minitablets (ODMTs), to describe the dose exposure in this patient population.

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 congenital heart disease (LENA-Work Package (WP)09 Trial), and 50 children with heart failure due to dilated cardiomyopathy (LENA-WP08 Trial) get treated with an optimal dose of enalapril ODMTs for up to 8 weeks after thorough, individualised titration and get invited to join the 10 months Safety Follow-up Study (LENA-WP10 Trial).

In this WP09 Trial children from age of newborn to less than 6 years, naive to enalapril treatment or switched from an Angiotensin-Converting-Enzyme (ACE)-Inhibitor pre-treatment, receive an Initial Dose to investigate the reaction over 8 hours before a decision on the first dose level is made. Always up to 7 days later a next higher dose is given at the hospital, the patient is supervised for 4 and then always 2 hours before a decision on the prescribed dose for the next dosing period is made. In this study a target dose similar to the adult target dose (20 mg enalapril in a 70 year old adult result in 0.282 mg/kg/day enalapril) is defined. Enalapril ODMTs of 0.25 mg and 1 mg strength are available to allow for an individual dose titration scheme.

Weight-dependently, pharmacokinetic (PK) and pharmacodynamic (PD) data are collected once in a full PK/PD day over 12, respectively 6 hours, and single PK/PD samples at each Dose Titration Visit and each bi-weekly Study Control Visit until the Last Visit after 8 weeks of treatment. Blood pressure and renal monitoring is performed at each visit before deciding on the dose level for the next treatment period.

Pharmacogenomics and metabolomics exploratory studies are added as a sub-study to better understand the underlying disease, its progression as well as the impact of the ACE-inhibition on cardiac outcome and renal function.

Conditions

Heart Failure; Congenital Heart Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Drug administration

Enalapril Orodispersible Minitablet (ODMT), 0.25 mg or 1 mg, administered 1x/day or 2x/day for up to 8 weeks

Group Type: EXPERIMENTAL

Enalapril Orodispersible Minitablet

Intervention Type: DRUG

8-weeks treatment, open, uncontrolled, PK/PD, acceptability and palatability assessments and safety assessments after Enalapril intake in form of 0.25 mg or 1 mg ODMTs

Interventions

Enalapril Orodispersible Minitablet

8-weeks treatment, open, uncontrolled, PK/PD, acceptability and palatability assessments and safety assessments after Enalapril intake in form of 0.25 mg or 1 mg ODMTs

Intervention Type: DRUG

Other Intervention Names

Enalapril ODMT

Eligibility Criteria

Inclusion Criteria

• Age from birth to less than 6 years.
• Male and female patients.
• Weight greater than 2.5 kg.
• Diagnosis of heart failure due to congenital heart disease requiring after-load reduction by drug therapy.
• Subjects may be naïve to ACE-Inhibitors.
• Subjects already on ACE-Inhibitors willing to switch to enalapril Orodispersible Minitablets.
• Patient and/or parent(s)/legal representative provided written informed consent and assent from the patient according to national legislation and as far as achievable from the child.

Exclusion Criteria

• Neonates if born < 37 weeks of gestation.
• Severe heart failure and/or end stage heart failure precluding introduction or continuation of ACE-Inhibitor.
• Too low blood pressure, e.g. ˂P5
• Uncorrected primary obstructive valvular disease, or significant systemic ventricular outflow obstruction, dilated restrictive or hypertrophic cardiomyopathy.
• Uncorrected severe peripheral stenosis of large arteries including severe coarctation of the aorta.
• Severe renal impairment with serum creatinine >2x Upper Limit of Normal (ULN) (according to the hospital's test methodology)
• History of angioedema.
• Hypersensitivity to ACE-Inhibitors.
• Concommitant medication:

• Dual ACE-Inhibitor therapy
• Renin inhibitors
• Angiotensin II antagonists
• Non-Steroidal Anti-Inflammatory Drugs (including ibuprofen) except for aspirin and paracetamol
• Already enrolled in an interventional trial with an investigational drug, unless no interference with the current study can be shown.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ethicare GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milica Bajcetic, Prof,MD,PhD

Role: STUDY_CHAIR

Univerzitetska Dečja Klinika Belgrade

Ida Jovanovic, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Univerzitetska Dečja Klinika Belgrade

Michiel Dalinghaus, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Sophia Children's Hospital, Erasmus MC Rotterdam

J.M.P. J Breur, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Wilhelmina Children's Hospital, University Medical Center Utrecht

Christoph Male, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Michael Burch, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital for Children NHS Trust London

András Szatmári, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology Budapest

Locations

Medical University of Vienna

Vienna, , Austria

Hungarian Paediatric Heart Centre, Göttsegen Gyorgy Hungarian Institute of Cardiology

Budapest, , Hungary

Sophia Children's Hospital, Erasmus MC

Rotterdam, , Netherlands

Wilhelmina Children's Hospital, University Medical Center Utrecht

Utrecht, , Netherlands

Univerzitetska Dečja Klinika

Belgrade, , Serbia

Great Ormond Street Hospital for Children NHS Trust

London, , United Kingdom

Countries

Austria; Hungary; Netherlands; Serbia; United Kingdom

Central Contacts

Stephanie Laeer, Prof,MD,PhD

Role: CONTACT

stephanie.laeer@uni-duesseldorf.de

+49 211 8110740

Ingrid Klingmann, MD,PhD

Role: CONTACT

iklingmann@pharmaplex.be

+32 2 784 36 93

Facility Contacts

Christoph Male, MD,PhD

Role: primary

christoph.male@meduniwien.ac.at

+ 43 1 40400 32320

Vanessa Swoboda, MD

Role: backup

v.swoboda@live.at

+ 43 1 40400 32320

Andras Szatmari, Prof,MD,PhD

Role: primary

szatmari@kardio.hu

+36 1 215 1220

Laszlo Ablonczy, MD

Role: backup

ablonczyl@gmail.com

+36 1 215 1220

Michiel Dalinghaus, MD,PhD

Role: primary

m.dalinghaus@erasmusmc.nl

+3110-7040704

Tjitske van der Zanden

Role: backup

t.vanderzanden@erasmusmc.nl

+3110-7040704

J.M.P. Breur J. Breur, MD,PhD

Role: primary

h.breur@umcutrecht.nl

+ 31 8875 540 02

Milica Bajcetic, Prof,MD,PhD

Role: primary

milica.bajcetic@udk.bg.ac.rs

38 1112060716

Ida Jovanovic, Prof,MD,PhD

Role: backup

idaj@rcub.bg.ac.rs

38 1112060716

Michael Burch, Prof,MD,PhD

Role: primary

michael.burch@gosh.nhs.uk

+44 020 7405 9200

Other Identifiers

2015-002396-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2015-602295-02

Identifier Type: -

Identifier Source: org_study_id