Hypertension
Conditions
Keywords
Hypertension, ABPM, systolic blood pressure, diastolic blood pressure, cardiovascular disease, aliskiren, telmisartan
Brief summary
This study was specifically designed to provide additional information on the mechanism of action of direct renin inhibition postulating the higher-level RAS cascade inhibition. The purpose of this study was to compare the prolonged efficacy and safety of aliskiren to that of telmisartan in mild to moderate hypertensive patients in the 24 hrs Ambulatory Blood Pressure Monitoring setting after a one week treatment withdrawal.
Interventions
DRUGAliskiren
Aliskiren 150 mg tablets taken orally daily. 1 tablet for the first two weeks followed by 2 tablets for 10 weeks.
DRUGTelmisartan
Telmisartan 40 mg capsules taken orally daily. 1 capsule the first 2 weeks followed by 2 capsules for 10 weeks.
Placebo to Aliskiren tablets taken orally daily. 1 Tablet for the first 2 weeks and 2 tablets during the no treatment (withdrawal) week.
DRUGPlacebo to Telmisartan
Placebo to Telmisartan capsule taken orally daily. 1 capsule for the first 2 weeks and 2 capsules during the no treatment (withdrawal) week.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mean sitting systolic blood pressure ≥ 140 mmHg and \< 180 mmHg * 24-hr mean ambulatory systolic blood pressure ≥ 135 mmHg
Exclusion criteria
* Severe hypertension defined as mean sitting systolic blood pressure ≥ 180 mmHg and/or mean sitting diastolic blood pressure ≥ 110 mmHg * Patients with Type 1 diabetes mellitus * Secondary hypertension of any etiology * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24 Hour (24-Hr) Mean Ambulatory Systolic Blood Pressure (MASBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 12 weeks, 13 weeks | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MASBP was calculated by taking the mean of all Ambulatory Systolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MASBP from the end of the active treatment to Day 7 of the treatment withdrawal period was calculated using a two way analysis of variance with treatment and region as factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24 Hour (24-hr) Mean Ambulatory Diastolic Blood Pressure (MADBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 12 weeks, 13 weeks | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MADBP was calculated by taking the mean of all Ambulatory Diastolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MADBP from the end of the active treatment to Day 7 of the withdrawal period was calculated using a two way analysis of variance with treatment and region as factors. |
| Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | Baseline, 13 weeks | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at Baseline (at Randomization) and at week 13 (day 7 of the withdrawal period). The 4 Hour MASBP and MADBP was calculated by taking the mean of all Ambulatory Blood Pressure readings during the 24 hour period. The difference of the 24 hour measurements from baseline to day 7 of the withdrawal period were calculated using a two way analysis of variance with treatment and region as factors and baseline as a covariate. |
| Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Baseline, 12 weeks, 13 weeks | Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 minutes apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msSBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors. |
| Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Baseline, 12 weeks, 13 weeks | Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 min. apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msDBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors. |
Countries
Brazil, Canada, Ecuador, Germany, Hungary, Malaysia, Mexico, Panama, Philippines, Singapore, Slovakia, South Korea, Spain, Turkey (Türkiye), United Kingdom, Venezuela
Participant flow
Pre-assignment details
1359 participants entered the Placebo Run-In phase which was 1-2 weeks in duration. Those participants completing the Placebo-Run-In Phase were randomized to receive either aliskiren 300 mg or telmisartan 80 mg.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren 300 mg Aliskiren tablets starting at a dose of 150 mg taken orally daily for 2 weeks followed by a dose of 300 mg taken orally for 10 weeks and placebo (withdrawal) for one week. Participants took Placebo to Aliskiren: 1 tablet for the first 2 weeks and 2 tablets during the one week withdrawal period. | 414 |
| Telmisartan 80 mg Telmisartan capsules starting at a dose of 40 mg taken orally daily for 2 weeks followed by a dose of 80 mg taken orally daily for 10 weeks and placebo (withdrawal) for one week. Participants took Placebo to Telmisartan: 1 capsule for the first 2 weeks and 2 capsules during the one week withdrawal period. | 408 |
| Total | 822 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 1 |
| Overall Study | Abnormal test procedure result(s) | 6 | 8 |
| Overall Study | Administrative problems | 0 | 2 |
| Overall Study | Adverse Event | 9 | 14 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Protocol deviation | 4 | 1 |
| Overall Study | Randomized but discontinued | 2 | 4 |
| Overall Study | Withdrawal by Subject | 22 | 16 |
Baseline characteristics
| Characteristic | Aliskiren 300 mg | Telmisartan 80 mg | Total |
|---|---|---|---|
| Age Continuous | 55.8 years STANDARD_DEVIATION 11.46 | 56.0 years STANDARD_DEVIATION 11.91 | 55.9 years STANDARD_DEVIATION 11.68 |
| Sex: Female, Male Female | 206 Participants | 178 Participants | 384 Participants |
| Sex: Female, Male Male | 208 Participants | 230 Participants | 438 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 411 | 32 / 403 |
| serious Total, serious adverse events | 3 / 411 | 5 / 403 |
Outcome results
Primary
Change in 24 Hour (24-Hr) Mean Ambulatory Systolic Blood Pressure (MASBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period
An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MASBP was calculated by taking the mean of all Ambulatory Systolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MASBP from the end of the active treatment to Day 7 of the treatment withdrawal period was calculated using a two way analysis of variance with treatment and region as factors.
Time frame: 12 weeks, 13 weeks
Population: ABPM Completer Set consisting of all participants in the Full Analysis set who had ABPM measurements at the end of the active treatment period and Day 7 of the treatment withdrawal period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg | Change in 24 Hour (24-Hr) Mean Ambulatory Systolic Blood Pressure (MASBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 2.70 mmHg | Standard Error 0.466 |
| Telmisartan 80 mg | Change in 24 Hour (24-Hr) Mean Ambulatory Systolic Blood Pressure (MASBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 6.51 mmHg | Standard Error 0.461 |
Secondary
Change in 24 Hour (24-hr) Mean Ambulatory Diastolic Blood Pressure (MADBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period
An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MADBP was calculated by taking the mean of all Ambulatory Diastolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MADBP from the end of the active treatment to Day 7 of the withdrawal period was calculated using a two way analysis of variance with treatment and region as factors.
Time frame: 12 weeks, 13 weeks
Population: ABPM Completer Set consisting of all participants in the Full Analysis set who had ABPM measurements at the end of the active treatment period and Day 7 of the treatment withdrawal period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg | Change in 24 Hour (24-hr) Mean Ambulatory Diastolic Blood Pressure (MADBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 2.09 mmHg | Standard Error 0.328 |
| Telmisartan 80 mg | Change in 24 Hour (24-hr) Mean Ambulatory Diastolic Blood Pressure (MADBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | 4.21 mmHg | Standard Error 0.324 |
Secondary
Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period
An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at Baseline (at Randomization) and at week 13 (day 7 of the withdrawal period). The 4 Hour MASBP and MADBP was calculated by taking the mean of all Ambulatory Blood Pressure readings during the 24 hour period. The difference of the 24 hour measurements from baseline to day 7 of the withdrawal period were calculated using a two way analysis of variance with treatment and region as factors and baseline as a covariate.
Time frame: Baseline, 13 weeks
Population: Full Analysis Set consisting of all participants randomized to treatment with measurements at baseline and day 7 of the withdrawal period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren 300 mg | Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | MASBP | -8.39 mmHg | Standard Error 0.542 |
| Aliskiren 300 mg | Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | MADBP | -5.05 mmHg | Standard Error 0.379 |
| Telmisartan 80 mg | Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | MASBP | -5.59 mmHg | Standard Error 0.539 |
| Telmisartan 80 mg | Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | MADBP | -3.44 mmHg | Standard Error 0.377 |
Secondary
Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period
Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 min. apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msDBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors.
Time frame: Baseline, 12 weeks, 13 weeks
Population: Full Analysis set consisting of all participants randomized to treatment. n1=participants with measurements at baseline and end of the active treatment period for the Double-blind Period. n2=participants with measurements at the end of the active treatment period and end of the treatment withdrawal period for the Treatment Interruption Period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren 300 mg | Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Double-Blind Period (n1=374,371) | -6.35 mmHg | Standard Error 0.453 |
| Aliskiren 300 mg | Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Treatment Interruption Period (n2=369,363) | 0.03 mmHg | Standard Error 0.388 |
| Telmisartan 80 mg | Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Double-Blind Period (n1=374,371) | -6.60 mmHg | Standard Error 0.453 |
| Telmisartan 80 mg | Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Treatment Interruption Period (n2=369,363) | 2.69 mmHg | Standard Error 0.392 |
Secondary
Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period
Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 minutes apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msSBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors.
Time frame: Baseline, 12 weeks, 13 weeks
Population: Full Analysis set consisting of all participants randomized to treatment. n1=participants with measurements at baseline and end of the active treatment period for the Double-blind Period. n2=participants with measurements at the end of the active treatment period and end of the treatment withdrawal period for the Treatment Interruption Period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren 300 mg | Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Double-Blind Period (n1=374,371) | -15.22 mmHg | Standard Error 0.744 |
| Aliskiren 300 mg | Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Treatment Interruption Period (n2=369,363) | 1.26 mmHg | Standard Error 0.652 |
| Telmisartan 80 mg | Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Double-Blind Period (n1=374,371) | -14.64 mmHg | Standard Error 0.744 |
| Telmisartan 80 mg | Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Treatment Interruption Period (n2=369,363) | 5.00 mmHg | Standard Error 0.658 |