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

A 6 Week, Randomized, Multicenter, Double-blind, Double-dummy Study to Evaluate the Dose Response of Valsartan on Blood Pressure Reduction in Children 1-5 Years Old With Hypertension, With or Without Chronic Kidney Disease, Followed by a 20 Week Open-label Titration Phase

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.

Study Overview

• Status: Completed
• Conditions: Pediatric Hypertension With or Without CKD
• Intervention / Treatment: Drug: VAL489; Drug: VAL489 matching placebo

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2020
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• Brazil
  • Campinas, Brazil, 13087-567
    • Novartis Investigative Site
  • Caxias do Sul, Brazil, 95070-561
    • Novartis Investigative Site
  • Porto Alegre, Brazil, 90610-000
    • Novartis Investigative Site
  • Parana
    • Curitibia, Parana, Brazil, 80250-060
      • Novartis Investigative Site
• France
  • Montpellier, France, 34059
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
• Guatemala
  • Guatemala, Guatemala, 01001
    • Novartis Investigative Site
  • Guatemala, Guatemala, 1010
    • Novartis Investigative Site
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1096
    • Novartis Investigative Site
  • Budapest, Hungary, H-1083
    • Novartis Investigative Site
  • Szeged, Hungary, 6725
    • Novartis Investigative Site
• Italy
  • Palermo, Italy, 90134
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • MI
    • San Donato Milanese, MI, Italy, 20097
      • Novartis Investigative Site
• Lithuania
  • Vinius, Lithuania, 08406
    • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-274
    • Novartis Investigative Site
  • Gdansk, Poland, 80-952
    • Novartis Investigative Site
  • Krakow, Poland, 30-663
    • Novartis Investigative Site
  • Lodz, Poland, 93-338
    • Novartis Investigative Site
  • Lublin, Poland, 20-093
    • Novartis Investigative Site
  • Poznan, Poland, 61-825
    • Novartis Investigative Site
  • Szczecin, Poland, 71-252
    • Novartis Investigative Site
  • Warszawa, Poland, 04-154
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valsartan 0.25 mg/kg; Valsartan oral solution 0.25mg/kg once daily + matching placebo of valsartan oral solution 4 mg/kg once daily for 6 weeks (period 1)	Drug: VAL489; Valsartan 3mg/kg oral solution; Other Names: Diovan; Drug: VAL489 matching placebo; Valsartan 3 mg/kg oral solution; Other Names: Diovan
Experimental: Valsartan 4 mg/kg; Valsartan oral solution 4 mg/kg once daily + matching placebo of valsartan oral solution 0.25 mg/kg once daily for 6 weeks (period 1)	Drug: VAL489; Valsartan 3mg/kg oral solution; Other Names: Diovan; Drug: VAL489 matching placebo; Valsartan 3 mg/kg oral solution; Other Names: Diovan
Experimental: Valsartan 1 mg/kg; Open-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.	Drug: VAL489; Valsartan 3mg/kg oral solution; Other Names: Diovan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Systolic Blood Pressure (MSBP) at Week 6 Endpoint	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	Baseline, week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Diastolic Blood Pressure (MDBP) at 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	Baseline, Week 6
Patients Achieving <90th Percentile for Age, Gender and Height at Week 6 Endpoint in Both MSBP and MDBP	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	Week 6
CKD Patients Achieving Urine Albumin Creatinine Ratio Percentage Reduction (UACR) >=25% at Week 6	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.	Week 6 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Jankauskiene A, Drozdz D, Wasilewska A, de Paula-Bernardes R, Glazer R, Valentin M, Tan M, Chiang Y, Bapatla K. Efficacy and safety of valsartan in children aged 1-5 years with hypertension, with or without chronic kidney disease: a randomized, double-blind study followed by open-label phase. Curr Med Res Opin. 2021 Dec;37(12):2113-2122. doi: 10.1080/03007995.2021.1982681. Epub 2021 Oct 9.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2012
• Primary Completion (Actual): January 24, 2017
• Study Completion (Actual): January 24, 2017

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: June 8, 2012
• First Posted (Estimate): June 12, 2012

Study Record Updates

• Last Update Posted (Actual): September 27, 2017
• Last Update Submitted That Met QC Criteria: August 28, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Hypertension; CKD; Pediatric
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan
• Other Study ID Numbers: CVAL489K2306; 2011-005991-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No