A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 6 months-5 years old with hypertension, followed by a 2 week placebo withdrawal period

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005261-19-BE
• Date of registration: 15/02/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 6 months-5 years old with hypertension, followed by a 2 week placebo withdrawal period
• Scientific title: A randomized, multicenter, double-blind, 6 week study to evaluate the dose response of valsartan on blood pressure reduction in children 6 months-5 years old with hypertension, followed by a 2 week placebo withdrawal period
• Date of first enrolment: 23/04/2007
• Target sample size: 75
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005261-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, France, Germany, Hungary, Italy, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients who are eligible and able to participate in the study and whose parent
(s)/guardian(s) consent in writing (written informed consent) to their doing so
after the purpose and nature of the investigation has been clearly explained.
2. Male or female between the ages of 6 months to 5 years, at visit 1 with a documented
history of hypertension.
3. Must be able to swallow the liquid formulation of the study medication
4. Must be = 8 kg or = 40 kg
5. Patients, either naïve or treated, must have a documented history of a mean
seated systolic blood pressure (mean of three measurements), equal to or
greater than 95th percentile (Appendix 3). For children under 1 year of age see appendix 4. For all patients, mean seated systolic blood pressure should be equal to or greater than 95th percentile at randomization.
6. Patients with uncontrolled blood pressure, receiving background antihypertensive
therapy, may continue on this therapy provided there is no change in dosing
regimen.
7. Parent(s)/guardian(s) are able to follow verbal and/or written instructions in the
local language.

Are the trial subjects under 18? yes
Number of subjects for this age range:
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:
For full list, please refer to protocol.
1. Patients whose mean seated systolic blood pressure (mean of three
measurements), at the baseline visit (Visit # 2) is = 25% higher than the 95th
percentile Appendix 3. For children under 1 year of age see Appendix 4.
2. Physical examination of patient demonstrates abnormalities that would make
this study medically hazardous to the patient.
3. Patients with background ARB therapy.
4. Patients that demonstrate any clinically significant abnormalities or clinically
noteworthy abnormal laboratory values (other than those relating to renal
function), including but not limited to the following:
• AST/SGOT or ALT/SGPT > 3 times the upper limit of the reference range
• Total bilirubin > 2 times the upper limit of the reference range
• Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz
formula to estimate glomerular filtration rate [GFR], see section 7.5.5 for
formula, based on the serum creatinine concentration obtained at Visit 1
(Screening).
• WBC count < 3000/mm³
• Platelet count < 100,000/mm³
• Serum potassium > upper limit of the reference range
5. Patients that demonstrate clinically significant ECG abnormalities other than
those associated with left ventricular hypertrophy and AV block controlled with a
pacemaker.
6. Patients that have coarctation of the aorta with a gradient of = 30 mm Hg, or
renal artery stenosis.
7. Patient that has any clinically significant unstable medical condition or chronic
disease that would put the patient at risk of experiencing an adverse event
associated with the expected pharmacodynamic effects of the study medication.
8. Patient that has experienced a significant clinical illness within 10 days prior to
baseline visit.
9. Patient that is known to have tested positive for the hepatitis B surface antigen
or hepatitis C antibody.
10. Patient that is known to have tested seropositive for the human
immunodeficiency virus (HIV) or patient is concomitantly receiving anti-retroviral
therapy.
11. Patients that had a previous solid organ transplantation < 1 year prior to Visit 1 is excluded. Patient whose transplantation was performed = 1 year prior to Visit 1 must be on stable doses of immunosuppresive therapy and deemed clinically stable by the clinician, to be enrolled. Stable doses of immunosuppressive therapy are defined as no change in frequency or total daily doses of immunosuppressive therapy for at least 3 months prior to screening . Doses of immunosuppressive therapy must be maintained throughout Periods 1 & 2 of the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hypertension

Intervention(s)

Trade Name: Diovan 160
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valsartan
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 160-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To evaluate the overall safety and tolerability of valsartan in 6 months to 5 year old
hypertensive children when treated for up to 6 weeks.
• To evaluate blood pressure change at the end of Period 2 from end of Period 1,
when comparing pooled valsartan patients versus pooled placebo patients.

Exploritory Objectives:
• Explore the change in blood pressure (MSSBP and MSDBP) from baseline to end of
Period 2 in the subpopulation of patients who continued on valsartan in both
Period 1 and Period 2.

Primary end point(s): Change from baseline in MSSBP (mean sitting systolic blood pressure)

The primary analysis is for change from baseline at the Period I endpoint in a dose dependent manner. Baseline is defined as the Week 0 value. The Period I endpoint is defined as the Week 6 value or the last post-baseline observation during Period I carried forward (LOCF).

Main Objective: To evaluate a dose dependent reduction in MSSBP when comparing three doses of valsartan (0.25 mg,/kg, 1 mg/kg and 4 mg/kg ) over a 6 week period in children
6 months-5 years old with hypertension ( = 95th percentile).

Secondary ID(s)

CVAL489K2303