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Efficacy, Safety and Tolerability of Multiple Doses of Valsartan in Children With Hypertension With or Without CKD

Phase 3
Completed
Conditions
Pediatric Hypertension With or Without CKD
Interventions
Drug: VAL489 matching placebo
Registration Number
NCT01617681
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

To assess efficacy, safety and tolerability of valsartan when comparing two doses of valsartan in reducing and controlling blood pressure in children with hypertension with or without CKD.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
127
Inclusion Criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

Have the ability to provide written informed consent; Have at baseline , a documented diagnosis of hypertension (as defined in the National High Blood Pressure Education Program 2004); MSBP (mean of 3 measurements) must be ≥95th percentile, and ≤25% above the 95th percentile, for age, gender and height, at baseline; CKD patients must be defined as any of the following criteria: Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: Abnormalities in the composition of urine, Abnormalities in imaging tests, Abnormalities on kidney biopsy, Estimated eGFR <60 mL/min/1.73m2 for ≥3 months, with or without the other signs of kidney damage described above; Able to swallow the valsartan solution; Body weight must be ≥8 kg and ≤40 kg at baseline; Must be able to safely washout from other antihypertensive therapy (if applicable) Exclusion criteria AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range; Estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m² (calculated using Modified Schwartz Formula); Serum potassium >5.3 mmol/L; Uncontrolled diabetes mellitus, as defined by the investigator; Unilateral, bilateral and graft renal artery stenosis; Current diagnosis of heart failure (NYHA Class II-IV); Patients taking any of the following concomitant medications following screening: RAAS blockers other than study drug, Lithium, Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels; Non-steroidal anti-inflammatory drugs (NSAIDS), including selective COX-2 inhibitors, acetylsalicylic acid >3g/day, and non-selective NSAIDs (paracetamol/acetaminophen is permitted); Antidepressant drugs in the class of MAO inhibitors (e.g. phenelzine); Chronic use of stimulant therapy for ADD/ADHD; patients who have coarctation of the aorta with a gradient of ≥30 mmHg; Previous solid organ transplantation except renal transplantation. Renal transplant must have occurred at least 1 year prior to enrollment; Patient must be on stable doses of immunosuppressive therapy and deemed clinically stable by the investigator; Patients known to be positive for the human immunodeficiency virus (HIV) Other protocol defined inclusion/exclusion criteria may apply.

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Valsartan 0.25 mg/kgVAL489Valsartan oral solution 0.25mg/kg once daily + matching placebo of valsartan oral solution 4 mg/kg once daily for 6 weeks (period 1)
Valsartan 1 mg/kgVAL489Open-label (Period 2) valsartan will be optionally titrated from 1 mg/kg to 2 mg/kg. Valsartan will continue to be optionally up titrated in 1 mg/kg increments every 4 weeks until maximum dose of 4 mg/kg is achieved. Duration 20 weeks.
Valsartan 0.25 mg/kgVAL489 matching placeboValsartan oral solution 0.25mg/kg once daily + matching placebo of valsartan oral solution 4 mg/kg once daily for 6 weeks (period 1)
Valsartan 4 mg/kgVAL489 matching placeboValsartan oral solution 4 mg/kg once daily + matching placebo of valsartan oral solution 0.25 mg/kg once daily for 6 weeks (period 1)
Valsartan 4 mg/kgVAL489Valsartan oral solution 4 mg/kg once daily + matching placebo of valsartan oral solution 0.25 mg/kg once daily for 6 weeks (period 1)
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Systolic Blood Pressure (MSBP) at Week 6 EndpointBaseline, week 6

Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) at Baseline and Week 6 endpoint in Period 1 Double Blind Phase

Secondary Outcome Measures
NameTimeMethod
Patients Achieving <90th Percentile for Age, Gender and Height at Week 6 Endpoint in Both MSBP and MDBPWeek 6

Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) Week 6

CKD Patients Achieving Urine Albumin Creatinine Ratio Percentage Reduction (UACR) >=25% at Week 6Week 6 weeks

UACR response is defined as percentage change from baseline in UACR≤ 25%. UACR \[mg/mmol\] = urine albumin \[mg/L\] / urine creatinine \[mmol/L\] UACR was collected for CKD patients only. The UACR value at a given visit for a patient was to be derived by the median of the three lab values collected for that visit Week 6.

Change From Baseline in Mean Diastolic Blood Pressure (MDBP) at Week 6Baseline, Week 6

Patient's blood pressure will be measured in the same position at every visit Systolic and diastolic blood pressures will be measured three times at 2-3 minute intervals. The arithmetic mean of these three blood pressure measurements will be used as the mean office blood pressure (MSBP and MDBP) Baseline and Week 6 endpoint in Period 1 Double Blind Phase

Trial Locations

Locations (1)

Novartis Investigative Site

🇵🇱

Warszawa, Poland

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