Pediatric Hypertension With or Without CKDPhase 3NCT01617681
Efficacy, Safety and Tolerability of Multiple Doses of Valsartan in Children With Hypertension With or Without CKD
A Phase 3 study testing VAL489 in people with Pediatric Hypertension With or Without CKD, run by Novartis Pharmaceuticals at 27 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 5 years
- Conditions the study is for
- Pediatric Hypertension With or Without CKD
- What is being tested?
- VAL489
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 27 sitesin 9 countries
- Study dates
- 8 Nov 2012to 24 Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
27 sites in 9 countries.
27 sites in 9 countries
Poland8 sites
Novartis Investigative Site
Bialystok, 15-274
Novartis Investigative Site
Gdansk, 80-952
Novartis Investigative Site
Krakow, 30-663
Novartis Investigative Site
Lodz, 93-338
Novartis Investigative Site
Lublin, 20-093
Novartis Investigative Site
Poznan, 61-825
Novartis Investigative Site
Szczecin, 71-252
Novartis Investigative Site
Warsaw, 04-154
Brazil4 sites
Novartis Investigative Site
Campinas, 13087-567
Novartis Investigative Site
Caxias do Sul, 95070-561
Novartis Investigative Site
Curitibia, Paraná, 80250-060
Novartis Investigative Site
Porto Alegre, 90610-000
Guatemala3 sites
Novartis Investigative Site
Guatemala City, 01001
Novartis Investigative Site
Guatemala City, 01010
Novartis Investigative Site
Guatemala City, 1010
Hungary3 sites
Novartis Investigative Site
Budapest, H 1096
Novartis Investigative Site
Budapest, H-1083
Novartis Investigative Site
Szeged, 6725
Italy3 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Palermo, 90134
Novartis Investigative Site
San Donato Milanese, MI, 20097
Belgium2 sites
Novartis Investigative Site
Antwerp, 2020
Novartis Investigative Site
Liège, 4000
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Marburg, 35039
About this study
Official title: 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.
- Being tested
- VAL489, VAL489 matching placebo
- Keywords
- Hypertension; CKD; Pediatric
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VAL489Drug
Also called Diovan
Valsartan 3mg/kg oral solution
VAL489 matching placeboDrug
Also called Diovan
Valsartan 3 mg/kg oral solution
| Study group | Role | What they receive |
|---|---|---|
| Valsartan 0.25 mg/kg | Experimental | Valsartan oral solution 0.25mg/kg once daily + matching placebo of valsartan oral solution 4 mg/kg once daily for 6 weeks (period 1) Receives: Drug: VAL489; Drug: VAL489 matching placebo |
| Valsartan 4 mg/kg | Experimental | 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) Receives: Drug: VAL489; Drug: VAL489 matching placebo |
| Valsartan 1 mg/kg | Experimental | 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. Receives: Drug: VAL489 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, week 6
Secondary outcomes (3)
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
Measured: 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
Measured: 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.
Measured: Week 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2012 (estimated)
- Study start8 Nov 2012
- Primary completion24 Jan 2017
- Study completion24 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric Hypertension With or Without CKDStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01617681
- Sponsor's protocol ID
- CVAL489K2306
- Other IDs
- 2011-005991-40
- Status last verified
- Aug 2017
- First submitted
- 6 Jun 2012
- Last updated
- 27 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
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.
PubMed 34543161
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01617681
- Acronym / sponsor ID
- CVAL489K2306
- Keywords
- Hypertension; CKD; Pediatric
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2012 (actual)
- Primary completion
- 24 Jan 2017 (actual)
- Study completion
- 24 Jan 2017 (actual)
- First posted
- 12 Jun 2012 (estimated)
- Results
- Posted 27 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Valsartan 0.25 mg/kg | Experimental | Drug: VAL489, Drug: VAL489 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/kg | Experimental | Drug: VAL489, Drug: VAL489 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 1 mg/kg | Experimental | Drug: VAL489Open-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. |
Who may qualify
- Ages
- 1 year to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VAL489Also: DiovanValsartan 3mg/kg oral solution | Drug | Valsartan 0.25 mg/kg, Valsartan 1 mg/kg, Valsartan 4 mg/kg |
| VAL489 matching placeboAlso: DiovanValsartan 3 mg/kg oral solution | Drug | Valsartan 0.25 mg/kg, Valsartan 4 mg/kg |
Primary outcome
Change From Baseline in Mean Systolic Blood Pressure (MSBP) at Week 6 Endpoint
Time frame: Baseline, 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
3 secondary outcomes
Change From Baseline in Mean Diastolic Blood Pressure (MDBP) at Week 6
Time frame: Baseline, Week 6
Patients Achieving <90th Percentile for Age, Gender and Height at Week 6 Endpoint in Both MSBP and MDBP
Time frame: Week 6
CKD Patients Achieving Urine Albumin Creatinine Ratio Percentage Reduction (UACR) >=25% at Week 6
Time frame: Week 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34543161Jankauskiene 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.
- Individual participant dataSharing planned: Undecided. 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
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
27 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VAL489 in people with Pediatric Hypertension With or Without CKD, run by Novartis Pharmaceuticals at 27 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Poland, Brazil, Guatemala, Hungary, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Mean Systolic Blood Pressure (MSBP) at Week 6 Endpoint (time frame: Baseline, week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01617681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.