Orodispersible Minitablets of Enalapril in Children With Heart Failure Due to Dilated Cardiomyopathy

NCT ID: NCT02652728

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 1 month to less than 12 years of age, suffering from heart failure due to dilated cardiomyopathy, 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 up 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 the 10 months Safety Follow-up Study (LENA-WP10 Trial).

In this WP08 Trial children between 1 month and less than 12 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 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 protocol a target dose similar to the adult target dose (20 mg of 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 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 ACE-inhibition on cardiac outcome and renal function.

Conditions

Heart Failure; Dilated Cardiomyopathy

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

Weight-dependent dose titration and long-term treatment scheme with enalapril ODMTs of 0.25 mg and 1 mg strength

Interventions

Enalapril Orodispersible Minitablet

Weight-dependent dose titration and long-term treatment scheme with enalapril ODMTs of 0.25 mg and 1 mg strength

Intervention Type: DRUG

Other Intervention Names

Enalapril ODMT

Eligibility Criteria

Inclusion Criteria

Patients presenting with heart failure with signs of left ventricular (LV) systolic dysfunction who are eligible to receive ACE-Inhibitors in addition to standard therapy (e.g., digitalis and diuretics) can be enrolled into this trial. Patients who previously presented with LV systolic dysfunction and who have already been treated with ACE-Inhibitors, and currently still have an indication for the use of an ACE-Inhibitor can be switched to an equivalent starting dose of enalapril ODMT.

• Age 1 month to less than 12 years.
• Male and female patients.
• Diagnosis of dilated cardiomyopathy presenting with LV end-diastolic dimension > P95 and/or LV shortening fraction (SF) < 25%
• Subjects may be naïve to ACE-Inhibitor.
• Subjects already on ACE-Inhibitor willing to switch to enalapril Orodispersible Minitablets.
• Written informed consent from parent(s)/legal representative and assent from the patient according to national legislation and as far as achievable from the child.

Exclusion Criteria

• Severe heart failure and/or end stage heart failure precluding introduction or continuation of ACE-Inhibitor.
• Too low blood pressure, e.g. ˂P5
• Restrictive and hypertrophic cardiomyopathies.
• Obstructive valvular disease (peak echocardiographic gradient more than 30 mm Hg).
• 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-Inhibitor.
• Concomitant 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 Month
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ethicare GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michiel Dalinghaus, MD, PhD

Role: STUDY_CHAIR

Sophia Children's Hospital Erasmus MC Rotterdam

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

Role: PRINCIPAL_INVESTIGATOR

Wilhelmina Children's Hosptial University Medical Center Utrecht

Ida Jovanovic, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Univerzitetska Decja Klinika Belgrade

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 London

András Szatmári, Prof,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Hungarian Paediatric Heart Institute, 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 7843692

Facility Contacts

Christoph Male, Prof,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

András Szatmári, 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

'Michiel Dalinghaus' <m.dalinghaus@erasmusmc.nl>

+3110-7040704

Tjitske van der Zanden

Role: backup

t.vanderzanden@erasmusmc.nl

+3110-7040704

J.M.P. 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

2015-002335-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2015-602295-01

Identifier Type: -

Identifier Source: org_study_id