Hypertension
Conditions
Keywords
Children, pediatrics, High Blood Pressure, Hypertension, Valsartan
Brief summary
The purpose of this study is to evaluate the safety and efficacy of three doses of valsartan (0.25, 1.0, and 4.0 mg/kg) on mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) in 6 months - 5 year old children with hypertension (sitting systolic blood pressure \[SSBP\] ≥ 95th percentile ).
Interventions
DRUGValsartan 0.25 mg/kg
once daily
DRUGValsartan 1.0 mg/kg
once daily
DRUGValsartan 4.0 mg/kg
once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
* Children aged 6 months - 5 years at Visit 1, with a documented history of hypertension * Must be able to swallow liquid formulation * Must be ≥ 6 kg or ≤ 40 kg at randomization * Must have documented history MSSBP (mean of 3 measurements) must be ≥ 95th percentile for age, gender and height, at randomization * If patients enter with uncontrolled BP they can remain on background antihypertensives with an unchanged dosing regimen * If patients have had a solid organ transplant more than 1 year ago they must be on stable doses of immunosuppressive therapy * Parent(s)/guardian(s) are able to follow verbal and/or written instructions in the local language
Exclusion criteria
* Patients with background ARB therapy * Patients demonstrating any clinically significant abnormalities or clinically noteworthy abnormal lab values (other than those relating to renal function) * AST/SGOT or ALT/SGPT \> 3 times the upper limit of the reference range * Glomerular filtration rate \< 30 mL/min/1.73m² * Serum potassium \> upper limit of the reference range * MSSBP ≥ 25% above the 95th percentile * Patients exhibiting clinically significant ECG abnormalities * Patients that have coarctation of the aorta with a gradient of ≥ 30 mm Hg, or renal artery stenosis Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Period 1 (Week 6) | baseline and week 6 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)to End of Period 1 (Week 6) | baseline and week 6 |
| Change From End of Period 1 (Week 6) in Mean Sitting Systolic Blood Pressure (MSSBP) to End of Placebo-controlled Withdrawal Period (Week 8) | week 6 and week 8 |
| Change From End of Period 1 (Week 6) in Mean Sitting Diastolic Blood Pressure (MSDBP) to End of Placebo-controlled Withdrawal Period (Week 8) | week 6 and week 8 |
Countries
Belgium, Brazil, France, Hungary, India, Italy, Poland, South Africa, Sweden, Turkey (Türkiye), United States
Participant flow
Recruitment details
At period 1, participants were randomized (2:1:2) to Valsartan 0.25 mg/kg, 1.0 mg/kg or 4.0 mg/kg. At period 2, participants were randomized (1:1) to either stay on Valsartan or switch to placebo.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Extemporaneous suspension of valsartan 0.25 mg/kg, taken once daily | 30 |
| Medium Dose Extemporaneous suspension of valsartan 1.0 mg/kg, taken once daily | 14 |
| High Dose Extemporaneous suspension of valsartan 4.0 mg/kg, taken once daily | 30 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 2 (2 Weeks) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Low Dose | Medium Dose | High Dose | Total |
|---|---|---|---|---|
| Age Continuous | 3.4 years STANDARD_DEVIATION 1.28 | 3.2 years STANDARD_DEVIATION 1.48 | 3.3 years STANDARD_DEVIATION 1.53 | 3.3 years STANDARD_DEVIATION 1.41 |
| Sex: Female, Male Female | 13 Participants | 4 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Male | 17 Participants | 10 Participants | 21 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 15 | 10 / 15 | 3 / 6 | 4 / 8 | 9 / 15 | 11 / 15 |
| serious Total, serious adverse events | 1 / 15 | 0 / 15 | 0 / 6 | 1 / 8 | 0 / 15 | 2 / 15 |
Outcome results
Primary
Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Period 1 (Week 6)
Time frame: baseline and week 6
Population: Analysis: Intention to Treat Imputation Technique: Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Period 1 (Week 6) | -8.3 mm Hg | Standard Deviation 10.44 |
| Medium Dose | Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Period 1 (Week 6) | -10.3 mm Hg | Standard Deviation 9.83 |
| High Dose | Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Period 1 (Week 6) | -14.4 mm Hg | Standard Deviation 10.93 |
Comparison: Slope change across all 3 active treatment groups.p-value: 0.09995% CI: [-2.31, 0.2]Regression, Linear
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)to End of Period 1 (Week 6)
Time frame: baseline and week 6
Population: Analysis: Intention to Treat Imputation Technique: Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)to End of Period 1 (Week 6) | -4.7 mm Hg | Standard Deviation 9.53 |
| Medium Dose | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)to End of Period 1 (Week 6) | -8.6 mm Hg | Standard Deviation 12.43 |
| High Dose | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)to End of Period 1 (Week 6) | -6.7 mm Hg | Standard Deviation 10.61 |
Secondary
Change From End of Period 1 (Week 6) in Mean Sitting Diastolic Blood Pressure (MSDBP) to End of Placebo-controlled Withdrawal Period (Week 8)
Time frame: week 6 and week 8
Population: Analysis: Intention to Treat Imputation Technique: Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change From End of Period 1 (Week 6) in Mean Sitting Diastolic Blood Pressure (MSDBP) to End of Placebo-controlled Withdrawal Period (Week 8) | 1.8 mm Hg | Standard Deviation 8.99 |
| Medium Dose | Change From End of Period 1 (Week 6) in Mean Sitting Diastolic Blood Pressure (MSDBP) to End of Placebo-controlled Withdrawal Period (Week 8) | 3.4 mm Hg | Standard Deviation 8.74 |
Secondary
Change From End of Period 1 (Week 6) in Mean Sitting Systolic Blood Pressure (MSSBP) to End of Placebo-controlled Withdrawal Period (Week 8)
Time frame: week 6 and week 8
Population: Analysis: Intention to Treat Imputation Technique: Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change From End of Period 1 (Week 6) in Mean Sitting Systolic Blood Pressure (MSSBP) to End of Placebo-controlled Withdrawal Period (Week 8) | 2.6 mm Hg | Standard Deviation 8.38 |
| Medium Dose | Change From End of Period 1 (Week 6) in Mean Sitting Systolic Blood Pressure (MSSBP) to End of Placebo-controlled Withdrawal Period (Week 8) | 4.1 mm Hg | Standard Deviation 9.66 |