Hypertension
Conditions
Keywords
Pediatric hypertension, primary hypertension, secondary, hypertension
Brief summary
The purpose of this study is to evaluate in a randomized, double-blind fashion, the long-term safety, tolerability and efficacy profile of aliskiren compared to the active comparator enalapril in children, 6 - 17 years old with hypertension (msSBP ≥ 95th percentile for age, gender and height, at baseline in study CSPP100A2365). Patients will be randomized to receive either aliskiren or enalapril. Weight-group based doses of aliskiren or enalapril will be administered once daily and children will receive study medication in a double-blind manner. This study is being conducted to support monotherapy registration of aliskiren for the treatment of hypertension in pediatric patients 6-17 years of age (age at baseline in Study CSPP100A2365).
Interventions
DRUGAliskiren
Low weight patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight patients: Starting dose 150 mg with optional titration to 300 and then 600 mg
DRUGEnalapril
Low weight patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight patients: Starting dose 10 mg with optional titration to 20 and then 40 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* msSBP (mean of 3 systolic blood pressure measurements) must be ≥ 95th percentile for age, gender and height, at Visit 2 (randomization), in study CSPP100A2365 * Must be ≥ 20 kg and ≤ 150 kg at Visit 2 (randomization), in study CSPP100A2365 * Must be able to swallow minitablets (2mm in diameter) administered in soft food * Successful completion of Phase 1 (dose response phase) and at least 1 week of Phase 2 (placebo withdrawal phase) of the CSPP100A2365 protocol, with no serious drug-related adverse event(s).
Exclusion criteria
* Patient receiving immunosuppressant medication (e.g. cyclosporine, MMF, etc) other than oral/topical steroids, for any medical condition * Current diagnosis of heart failure (NYHA Class II-IV) or history of cardiomyopathy or obstructive valvular disease * msSBP ≥ 25% above the 95th percentile * Second or third degree heart block without a pacemaker * 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 \[GFR\]), based on the serum creatinine concentration obtained at the screening visit) * WBC count \< 3000/mm³ * Platelet count \< 100,000/mm³ * Serum potassium \> 5.2 mEq/L * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study | Baseline - end of study (Week 52 or Last observation carried forward (LOCF) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study | Baseline - end of study (Week 52 or Last observation carried forward (LOCF) | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit. |
| Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study | Baseline to end of study (Week 52 or LOCF) | MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of diastolic blood pressure (DBP) and one third of difference between systolic blood pressure (SBP) and DBP i.e. MAP = DBP+1/3\*(SBP--DBP). |
Countries
Guatemala, Hungary, Poland, Puerto Rico, Slovakia, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Patients will receive one of the following doses based on the their weight: Low weight (≥20 to \<50 kg) patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight (≥50 to \<80 kg) patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight (≥80 to ≤150 kg) patients: Starting dose 150 mg with optional titration to 300 and then 600 mg | 104 |
| Enalapril Patients will receive one of the following doses based on their weight: Low weight (≥20 to \<50 kg) patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight (≥50 to \<80 kg) patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight (≥80 to ≤150 kg) patients: Starting dose 10 mg with optional titration to 20 and then 40 mg | 104 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 1 |
| Overall Study | Administrative problems | 1 | 1 |
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Protocol deviation | 2 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Aliskiren | Enalapril | Total |
|---|---|---|---|
| Age, Continuous | 11.7 years STANDARD_DEVIATION 3.4 | 11.9 years STANDARD_DEVIATION 3.4 | 11.8 years STANDARD_DEVIATION 3.39 |
| Age, Customized Adolescents 12 - 17 years | 54 participants | 53 participants | 107 participants |
| Age, Customized Children 6 - 11 years | 50 participants | 51 participants | 101 participants |
| Sex: Female, Male Female | 40 Participants | 32 Participants | 72 Participants |
| Sex: Female, Male Male | 64 Participants | 72 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 105 | 51 / 103 |
| serious Total, serious adverse events | 3 / 105 | 12 / 103 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit.
Time frame: Baseline - end of study (Week 52 or Last observation carried forward (LOCF)
Population: Full analysis set (FAS) included all randomized patients for this trial
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study | -7.63 millimeter(s) of mercury (mmHg) | Standard Error 1.16 |
| Enalapril | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study | -7.94 millimeter(s) of mercury (mmHg) | Standard Error 1.14 |
p-value: 0.004ANCOVA
Secondary
Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study
MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of diastolic blood pressure (DBP) and one third of difference between systolic blood pressure (SBP) and DBP i.e. MAP = DBP+1/3\*(SBP--DBP).
Time frame: Baseline to end of study (Week 52 or LOCF)
Population: Full analysis set (FAS) included all randomized patients for this trial
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study | -5.15 mmHg | Standard Error 0.89 |
| Enalapril | Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study | -5.95 mmHg | Standard Error 0.87 |
Secondary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study
Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit.
Time frame: Baseline - end of study (Week 52 or Last observation carried forward (LOCF)
Population: Full analysis set (FAS) included all randomized patients for this trial
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study | -3.90 mmHg | Standard Error 0.87 |
| Enalapril | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study | -4.94 mmHg | Standard Error 0.85 |