Hypertension
Conditions
Keywords
Children, pediatrics, High Blood Pressure, Hypertension, Valsartan, enalapril
Brief summary
The purpose of this 12-week active controlled trial is to evaluate the safety and efficacy of valsartan 80/160/320 mg (weight stratified) compared with enalapril 10/20/40 mg (weight stratified) on sitting systolic blood pressure (SSBP) in 6 - 17 year old children with hypertension (SSBP ≥ 95th percentile for age gender and height).
Interventions
DRUGValsartan
Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.
DRUGEnalapril
Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, ages 6-17, with a documented history of hypertension * Must be able to swallow a pill * Must be ≥ 18 kg or ≤160 kg * MSSBP (mean of 3 measurements) must be ≥ 95th percentile, for age, gender and height, at Visit 2 (randomization), by office blood pressure measurement * 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 to them. (An assent will be required for some patients depending upon their age and local requirements regarding assents)
Exclusion criteria
* Renal artery stenosis * Current diagnosis of heart failure (NYHA Class II-IV). * MSSBP ≥ 25% above the 95th percentile * Second or third degree heart block without a pacemaker. * Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. * Clinically significant valvular heart disease. * Patient that demonstrates clinically significant ECG abnormalities other than those associated with left ventricular hypertrophy. * Previous solid organ transplantation except renal, liver or heart transplantation. Renal, liver or heart transplant must have occurred at least 6 months prior to enrollment. Patient must be on stable doses of immunosuppressive therapy for 3 months and deemed clinically stable by the investigator. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | Baseline and Week 12 | Mean sitting systolic blood pressure (MSSBP) change after 12 weeks of treatment measured by office blood pressure measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | Baseline and Week 12 | The change from baseline in mean sitting diastolic blood pressure (MSDBP) after 12 weeks of treatment as measured by office blood pressure. |
| Decrease in MSSBP to < 95th Percentile for Age, Gender and Height | at week 12 | The percentage of children whose MSSBP decreased to \<95th percentile for age, gender, and height on valsartan vs. enalapril monotherapy at week 12. |
| Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients | Baseline and Week 8 | The effect of valsartan and enalapril between baseline and visit 6 on 24-hour mean ambulatory systolic and diastolic blood pressure (ASBP, ADBP) in a subset of patients. |
Countries
Belgium, France, Germany, Hungary, India, Italy, Poland, Slovakia, Sweden, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valsartan Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg. | 151 |
| Enalapril Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg. | 149 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory values | 0 | 1 |
| Overall Study | Adverse Event | 7 | 0 |
| Overall Study | Condition no longer requires study drug | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Valsartan | Enalapril | Total |
|---|---|---|---|
| Age Continuous | 12.7 years STANDARD_DEVIATION 2.93 | 13.0 years STANDARD_DEVIATION 2.94 | 12.9 years STANDARD_DEVIATION 2.93 |
| Sex: Female, Male Female | 65 Participants | 44 Participants | 109 Participants |
| Sex: Female, Male Male | 86 Participants | 105 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 151 | 52 / 148 |
| serious Total, serious adverse events | 3 / 151 | 2 / 148 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)
Mean sitting systolic blood pressure (MSSBP) change after 12 weeks of treatment measured by office blood pressure measurement.
Time frame: Baseline and Week 12
Population: Intent-to-treat. Only patients who had both baseline and endpoint values are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | -15.4 mm Hg | Standard Error 1.29 |
| Enalapril | Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) | -14.1 mm Hg | Standard Error 1.28 |
95% CI: [-3.8, 1.17]ANOVA
Secondary
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients
The effect of valsartan and enalapril between baseline and visit 6 on 24-hour mean ambulatory systolic and diastolic blood pressure (ASBP, ADBP) in a subset of patients.
Time frame: Baseline and Week 8
Population: A subset of approximately 100 - 150 patients from selected centers was expected to undergo Ambulatory Blood Pressure Monitoring at baseline (Week 0) and at Week 8; however, only 56 patients chose to participate in this aspect of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valsartan | Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients | ASBP | -9.8 mm Hg | Standard Deviation 6.75 |
| Valsartan | Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients | ADBP | -9.3 mm Hg | Standard Deviation 6.27 |
| Enalapril | Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients | ASBP | -6.8 mm Hg | Standard Deviation 7.41 |
| Enalapril | Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients | ADBP | -5.5 mm Hg | Standard Deviation 5.73 |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)
The change from baseline in mean sitting diastolic blood pressure (MSDBP) after 12 weeks of treatment as measured by office blood pressure.
Time frame: Baseline and Week 12
Population: Intent-to-treat. Only patients who had both baseline and endpoint values are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | -9.4 mm Hg | Standard Error 0.94 |
| Enalapril | Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) | -8.5 mm Hg | Standard Error 0.95 |
Secondary
Decrease in MSSBP to < 95th Percentile for Age, Gender and Height
The percentage of children whose MSSBP decreased to \<95th percentile for age, gender, and height on valsartan vs. enalapril monotherapy at week 12.
Time frame: at week 12
Population: Intent-to-treat. Only patients who had both baseline and endpoint values are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan | Decrease in MSSBP to < 95th Percentile for Age, Gender and Height | 66.9 Percentage of participants |
| Enalapril | Decrease in MSSBP to < 95th Percentile for Age, Gender and Height | 70.3 Percentage of participants |