Dose Titration of Lisinopril in Children Aged 1 to 18 Years With Primary or Secondary Hypertension

Study Overview
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Brief Summary
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This open label 4 month study will evaluate efficacy (blood pressure lowering effects) and safety of lisinopril in children 1-18y whose parents grant permission to participate. This dose titration study is being conducted to support the statement that personalized titration of lisinopril (based on blood pressure and renin-aldosterone ratio) can increase patient response.

Official Title
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Dose Titration Study to Test Efficacy and Safety of Lisinopril in Children Aged 1 to 18 Years With Primary or Secondary Hypertension.

Conditions
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Primary Hypertension, Secondary Hypertension

Intervention / Treatment
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* Drug: lisinopril, ACE-inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parental consent must be granted Patient age: 1y - 18 y Documented diagnosis of hypertension as defined in the National Heart, Lung and Blood Institute (NHBLI) 4th report, 2004 No reversible cause found on diagnostic work-up for hypertension Children older than 6y: 24h blood pressure monitoring confirms the diagnosis of hypertension Exclusion Criteria: Pregnancy Sexually active girls can only be included in the trial if they use an adequate form of birth control; during and until 30 days after ending the trial Following abnormal laboratory values: Hyperkaliemia (serum potassium > 5.3mmol/L); Anemia (hemoglobin < 8g/dL); AST or ALT > 3 times the upper limit of reference range; Total bilirubin > 3 times the upper limit of reference range Abnormalities of the oral cavity that can influence intake of medication Known sensitivity to ACE-inhibitors Known lactose intolerance History of angioedema Unilateral or bilateral stenosis of the renal artery Diagnosis of heart failure (NYHA Class II-IV) History of coarctation of the aorta Current treatment with: other drugs influencing the renin-angiotensin-aldosterone system; lithium; potassium sparing diuretics; non-steroidal anti-inflammatory drugs; aspirin; oral antidiabetic medication

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lisinopril<br>dose titration of investigational product (lisinopril) dependant on blood pressure, levels of renin and aldosterone and on adverse events. | Drug: lisinopril, ACE-inhibitor<br>* Lisinopril 0.1mg/kg/d, titration with + 0.1mg/kg/d. Max; daily dose: 0.4mg/kg. CAVE: dose reduction in case of renal impairment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentrations will be assessed after every dose titration |  | trough and 4 hours post dosing | 
| Adverse events with assessment of specific blood parameters | sodium, potassium, creatinine, bilirubin, aspartate transaminase/alanine transaminase (AST/ALT) and blood count | up to 4 months |