Heart Failure due to Congenital Heart Disease MedDRA version: 18.1 Level: LLT Classification code 10010495 Term: Congenital heart disease NOS System Organ Class: 100000004850
Conditions
Sponsors
Ethicare GmbH
Eligibility
Sex/Gender
All
Inclusion 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 (ACEI). • Subjects already on ACE-Inhibitors willing to switch to Enalapril Orodispersable Minitablets. • Patient and/or parent(s)/legal representative provided written informed consent. Permitted: Other CHF medications are allowed, at the discretion of the investigator. These include but are not limited to diuretics, beta-blockers, digoxin, mineralocorticoid receptor antagonist, aspirin. Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Neonates if born 2x ULN (Upper Limit of Normal) according to the hospital’s test methodology). • History of Angioedema. • Hypersensitivity to ACEI. • Concomittant medication: o Dual ACEI therapy o Renin inhibitors o Angiotensin II antagonists o NSAIDs except for aspirin acetylsalicylic acid only for antiplatelet therapy • Already enrolled in an interventional trial with an investigational drug, unless no interference with the current study can be shown.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To obtain paediatric pharmacokinetic data of enalapril and its active metabolite enalaprilat in patients treated with enalapril ODMTs to describe the dose exposure in the paediatric population with CHD. ;Secondary Objective: • To demonstrate safety, in particular renal safety, of enalapril ODMTs in children with CHD. • To characterise the dose/safety relationship from a starting dose to an optimal maintenance dose. • To explore the dose exposure/response relationship with pharmacodynamic parameters in the paediatric population with CHD. • To investigate the Shortening Fraction (SF) of the heart muscle by echocardiography. • To investigate the acceptability and palatability of enalapril ODMTs in the paediatric population with CHD. ;Primary end point(s): The bioavailability of enalapril and its active metabolite enalaprilat in young children (AUC from 0 to time of last sampling point, Cmax and Tmax); descriptive pharmacokinetic investigation. ;Timepoint(s) of evaluation of this end point: PK/PD profile sampling timepoints: Visit day 1: pre-dose, 0h, 2, 4, 6, 8, 12 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The bioavailability of enalapril and its active metabolite enalaprilat in the different age subsets (0 to ?12 months and 12 months to ?6 years) of the paediatric study population (AUC from 0 to time of last sampling point, Cmax and Tmax); descriptive pharmacokinetic investigation. 2. Markers of the renin-angiotensin-aldosterone system as exploratory pharmaco-dynamic investigation. 3. Brain natriuretic peptides (BNPs). 4. Acceptability and palatability of the novel formulation. 5. Safety parameters including blood pressure and renal function. 6. Echocardiography (Shortening Fraction) 7. Rehospitalisation due to heart failure. 8. Death due to worsening of the underlying disease. 9. Pharmacodynamic and efficacy endpoints analysis to differentiate high and low output disease. ;Timepoint(s) of evaluation of this end point: Biochemistry, Urine and BNP collected during each visit in the hospital to monitor renal function. PK and PD 1 sample collected during each visit, unless the patient terminated use of the IMP, then only PD sample is collected. Acceptability and Palatability questionnaire is completed during initial visit, once stable dose is reached and during end of study visit. | — |
Countries
Austria, Germany, Hungary, Netherlands, Serbia, United Kingdom
Contacts
Public ContactLead Clinical Project Manager
Pharmaplex bvba
Outcome results
None listed