Hypertension
Conditions
Keywords
hypertension, systolic blood pressure, exercise test, cardiovascular disease, aliskiren, valsartan
Brief summary
This study compared the blunting effect of aliskiren and valsartan monotherapies on exercise-induced rises in systolic blood pressure in patients with mild to moderate essential hypertension.
Interventions
DRUGAliskiren
Aliskiren was supplied in 150 mg tablets.
DRUGValsartan
Valsartan was supplied in 160 mg capsules.
Placebo to aliskiren was supplied in tablets matching aliskiren 150 mg.
Placebo to valsartan was supplied in capsules matching valsartan 160 mg.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mean sitting systolic blood pressure ≥ 140 mmHg and \< 180 mmHg measured at rest * Patients able to exercise and to reach 85% of their predicted heart rate during a standard exercise test on a treadmill according to the Bruce Protocol
Exclusion criteria
* Patients not confident in exercising or not able to exercise * Absolute contraindication to exercise * Mean sitting systolic blood pressure ≥ 180 mmHg and/or mean sitting diastolic blood pressure ≥ 110 mmHg measured at rest Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 After a Missed Dose | Baseline and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints. | The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 + 2 days (24-hrs after a missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 | Baseline and Week 8 (end of active treatment). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints. | The difference in resting vs. peak (85% of the maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 (end of active treatment); the change in SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate. |
| Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Week 8 (End of Active Treatment) to 24-hours After a Missed Dose | Week 8 (Last dose; end of active treatment) and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints. | The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. The SBP at rest vs peak HR was recorded at Week 8 (end of active treatment) and Week 8 + 2 days (48-hrs after last dose; 24-hrs after missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate. |
Countries
Czechia, Hungary, Singapore, United Kingdom
Participant flow
Recruitment details
All patients underwent a 2-week washout and a 1-2 week single blind placebo run in. Eligible patients then performed the treadmill exercise test for randomization according to the Bruce Protocol. Patients capable of reaching the defined peak exercise (85% of their predicted HR) were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren For the first week of the 8 week treatment period, patients received aliskiren 150 mg, placebo to aliskiren, and 2 capsules of placebo to valsartan. For the remaining 7 weeks of the study, patients received aliskiren 300 mg (two 150 mg tablets) and 2 capsules of placebo to valsartan. The tablets and capsules (2 of each) were taken orally once daily each morning. To evaluate a missed dose, the last dose of medication was administered at the clinic, and the patient was scheduled to return 2 days later for exercise testing (8 weeks + 2 days). | 33 |
| Valsartan For the first week of the 8 week treatment period, patients received valsartan 160 mg, placebo to valsartan, and 2 tablets of placebo to aliskiren. For the remaining 7 weeks of the study, patients received valsartan 320 mg (two 160 mg capsules) and 2 tablets of placebo to aliskiren. The tablets and capsules (2 of each) were taken orally once daily each morning. To evaluate a missed dose, the last dose of medication was administered at the clinic, and the patient was scheduled to return 2 days later for exercise testing (8 weeks + 2 days). | 35 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unsatisfactory therapeutic effect | 1 | 2 |
Baseline characteristics
| Characteristic | Aliskiren | Valsartan | Total |
|---|---|---|---|
| Age Continuous | 58 years STANDARD_DEVIATION 6.3 | 60 years STANDARD_DEVIATION 8.3 | 59 years STANDARD_DEVIATION 7.4 |
| Sex: Female, Male Female | 14 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Male | 19 Participants | 27 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 33 | 4 / 35 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 |
Outcome results
Primary
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 After a Missed Dose
The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 + 2 days (24-hrs after a missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.
Time frame: Baseline and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.
Population: The Full Analysis Set (FAS) consisted of all patients who were randomized and took at least one dose of study drug. The Exercise Evaluable Set (EES) included all patients included in the FAS for whom the treadmill test values for SBP at peak were available at baseline and after a missed dose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 After a Missed Dose | 2.58 mmHg | Standard Error 3.54 |
| Valsartan | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 After a Missed Dose | 8.26 mmHg | Standard Error 3.48 |
Secondary
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8
The difference in resting vs. peak (85% of the maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 (end of active treatment); the change in SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.
Time frame: Baseline and Week 8 (end of active treatment). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.
Population: The Full Analysis Set (FAS) consisted of all patients who were randomized and took at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 | 5.78 mmHg | Standard Error 3.22 |
| Valsartan | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 | 7.79 mmHg | Standard Error 3.18 |
Secondary
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Week 8 (End of Active Treatment) to 24-hours After a Missed Dose
The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. The SBP at rest vs peak HR was recorded at Week 8 (end of active treatment) and Week 8 + 2 days (48-hrs after last dose; 24-hrs after missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.
Time frame: Week 8 (Last dose; end of active treatment) and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.
Population: The Full Analysis Set (FAS) consisted of all patients who were randomized and took at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Week 8 (End of Active Treatment) to 24-hours After a Missed Dose | -4.16 mmHg | Standard Error 3.28 |
| Valsartan | Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Week 8 (End of Active Treatment) to 24-hours After a Missed Dose | 1.37 mmHg | Standard Error 3.16 |