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

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Brief Title

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

Official Title

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

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.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Area under the Curve (AUC) of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in children with heart failure

Secondary Outcome

 AUC of enalapril and its active metabolite enalaprilat after administration of enalapril ODMTs in children with heart failure of two age-subsets


Heart Failure


Enalapril Orodispersible Minitablet

Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 2016

Completion Date

June 2017

Primary Completion Date

June 2017

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.

        Patients fulfilling the following inclusion criteria can be enrolled

          -  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

          -  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:

        Patients fulfilling any of the following exclusion criteria cannot be enrolled into this

          -  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.




1 Month - 11 Years

Accepts Healthy Volunteers



Michiel Dalinghaus, MD, PhD, +49 211 8110740, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Ethicare GmbH

Study Sponsor

Michiel Dalinghaus, MD, PhD, Study Chair, Sophia Children's Hospital Erasmus MC Rotterdam

Verification Date

January 2016