Trial Outcomes & Findings for Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients (NCT NCT01042392)
NCT ID: NCT01042392
Last Updated: 2012-04-03
Results Overview
The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
506 participants
Primary outcome timeframe
Baseline to 8 weeks
Results posted on
2012-04-03
Participant Flow
Participant milestones
| Measure |
Ramipril
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Ramipril
In period III (double-blind withdrawal): At visit 4, part of the patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Period II(Randomized,Double Blinded,8wk)
STARTED
|
257
|
0
|
249
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
Intent to Treat (ITT)
|
222
|
0
|
222
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
COMPLETED
|
247
|
0
|
241
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
NOT COMPLETED
|
10
|
0
|
8
|
0
|
|
Period III (Unblinded,Controlled, 1 Day)
STARTED
|
129
|
118
|
119
|
122
|
|
Period III (Unblinded,Controlled, 1 Day)
Per Protocol Missed-dose (PPMD)
|
98
|
73
|
93
|
82
|
|
Period III (Unblinded,Controlled, 1 Day)
COMPLETED
|
127
|
117
|
115
|
121
|
|
Period III (Unblinded,Controlled, 1 Day)
NOT COMPLETED
|
2
|
1
|
4
|
1
|
Reasons for withdrawal
| Measure |
Ramipril
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Ramipril
In period III (double-blind withdrawal): At visit 4, part of the patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Period II(Randomized,Double Blinded,8wk)
Adverse Event
|
6
|
0
|
5
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
Unsatisfactory therapeutic effect
|
1
|
0
|
0
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
Withdrawal by Subject
|
1
|
0
|
2
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
Lost to Follow-up
|
0
|
0
|
1
|
0
|
|
Period II(Randomized,Double Blinded,8wk)
Administrative problems
|
2
|
0
|
0
|
0
|
|
Period III (Unblinded,Controlled, 1 Day)
Adverse Event
|
0
|
0
|
1
|
0
|
|
Period III (Unblinded,Controlled, 1 Day)
Protocol Violation
|
2
|
0
|
0
|
0
|
|
Period III (Unblinded,Controlled, 1 Day)
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
|
Period III (Unblinded,Controlled, 1 Day)
Administrative problems
|
0
|
1
|
1
|
1
|
Baseline Characteristics
Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients
Baseline characteristics by cohort
| Measure |
Ramipril
n=257 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=249 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Total
n=506 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
59.8 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
61.0 years
STANDARD_DEVIATION 11.4 • n=7 Participants
|
60.4 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Age, Customized
< 50 years
|
56 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Age, Customized
50 - 64 years
|
119 Participants
n=5 Participants
|
115 Participants
n=7 Participants
|
234 Participants
n=5 Participants
|
|
Age, Customized
65 - 74 years
|
56 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Age, Customized
>= 75 years
|
26 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
142 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
275 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
115 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
231 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 8 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5.
The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.
Outcome measures
| Measure |
Ramipril
n=213 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=213 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
|
-18.80 mmHg
Standard Error 0.92
|
-20.78 mmHg
Standard Error 0.92
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 8 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at both time points were included in this analysis.
The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of variance included treatment factor and baseline value of mean sitting DBP as covariable.
Outcome measures
| Measure |
Ramipril
n=213 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=213 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
|
-5.23 mmHg
Standard Error 0.60
|
-6.39 mmHg
Standard Error 0.60
|
—
|
—
|
SECONDARY outcome
Timeframe: At 4 and 8 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at each time point were included in this analysis.
The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. Controlled blood pressure (BP) is defined as mean office systolic BP/ diastolic BP \< 140/90 mmHg.
Outcome measures
| Measure |
Ramipril
n=222 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=222 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Percentage of Patients With Controlled Blood Pressure
At week 4 (N= 218, 217)
|
36.7 Percentage
|
40.1 Percentage
|
—
|
—
|
|
Percentage of Patients With Controlled Blood Pressure
At week 8 (N= 213, 213)
|
26.8 Percentage
|
32.4 Percentage
|
—
|
—
|
SECONDARY outcome
Timeframe: After 8 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM to evaluate the occurrence or absence of a morning peak were included in this analysis.
Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the day before visit 4, the device attached to the ambulatory blood pressure non-dominant arm of the patient. The BP morning surge was defined as the average of the measurements taken during the first 2 hours after waking the patient. The minimal night blood pressure was defined as the average of the two lowest BP measures (the lowest hourly average) recorded during night time.
Outcome measures
| Measure |
Ramipril
n=114 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=112 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Number of the Participants With More Than 55 mmHg Difference Between the Mean SBP Measured at the Morning Surge and the Mean Minimal SBP Measured During the Night
|
3 Participants
|
9 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 4 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5.
The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.
Outcome measures
| Measure |
Ramipril
n=218 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=217 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Change in msSBP and msDBP From Visit 2 (Baseline) to Visit 3 (at 4 Weeks)
Change in msSBP
|
-19.42 mmHg
Standard Error 0.92
|
-19.75 mmHg
Standard Error 0.92
|
—
|
—
|
|
Change in msSBP and msDBP From Visit 2 (Baseline) to Visit 3 (at 4 Weeks)
Change in msDBP
|
-5.37 mmHg
Standard Error 0.56
|
-5.60 mmHg
Standard Error 0.56
|
—
|
—
|
SECONDARY outcome
Timeframe: At week 8Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM measurements over 24 hours were included in this analysis.
Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the eve of visit 4 (week 8), the device attached to the ambulatory blood pressure non-dominant arm of the patient. The difference between mean-hour maximum SBP mean-hour minimum SBP between 1 am and 8 am was measured.
Outcome measures
| Measure |
Ramipril
n=175 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=186 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Difference Between the Maximal and the Minimal Mean-hour SPB Measured Between 1 and 8 am at Week 8
|
33.6 mmHg
Standard Deviation 14.04
|
35.5 mmHg
Standard Deviation 15.05
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 8 weeksPopulation: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at different categories were included in this analysis.
The sub-groups were: "Riser" = patients with \>= 55 mmHg difference between the mean SPB measured at the morning surge and the mean minimal SBP measured during the night. The "Non-risers" in whom the difference is \<55 mmHg. Patients called "dippers" in whom there was a decrease in average nocturnal SBP ≥ 10% compared with average daytime SBP, in contrast to patients "non-dippers " in whom this difference was \<10%.
Outcome measures
| Measure |
Ramipril
n=222 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=222 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msSBP: Risers (n= 3, 9)
|
-19.7 mmHg
Standard Deviation 6.11
|
-16.9 mmHg
Standard Deviation 10.52
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msSBP: Non-risers (n=109, 103)
|
-19.2 mmHg
Standard Deviation 13.99
|
-20.5 mmHg
Standard Deviation 14.49
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msSBP: Dippers (n= 80, 94)
|
-18.1 mmHg
Standard Deviation 11.86
|
-19.8 mmHg
Standard Deviation 12.05
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msSBP: Non-dippers (n= 93, 92)
|
-19.2 mmHg
Standard Deviation 14.93
|
-21.1 mmHg
Standard Deviation 15.06
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msDBP: Risers (n= 3, 9)
|
-7.3 mmHg
Standard Deviation 10.60
|
-6.6 mmHg
Standard Deviation 9.11
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msDBP: Non-risers(n=109, 103)
|
-4.2 mmHg
Standard Deviation 9.51
|
-5.7 mmHg
Standard Deviation 9.61
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msDBP: Dippers (n= 80, 94)
|
-5.5 mmHg
Standard Deviation 9.63
|
-6.3 mmHg
Standard Deviation 9.81
|
—
|
—
|
|
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)
Change in msDBP: Non-dippers (n= 93, 92)
|
-5.3 mmHg
Standard Deviation 9.59
|
-6.5 mmHg
Standard Deviation 9.56
|
—
|
—
|
SECONDARY outcome
Timeframe: From 8 weeks to 48 hours after week 8Population: Per-protocol missed dose population included all per protocol population patients who had received the study treatment for period 3 according to the protocol (duration of period 3 and treatment intake). Patients with observation at both time points were included in this analysis.
The change in blood pressure was measured between visit 4 (end of the period of double-blind active treatment which was at week 8) and visit 5 (48 hours after the last active dose taken) in the group of patients who received aliskiren or placebo and those who received ramipril or placebo. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.
Outcome measures
| Measure |
Ramipril
n=95 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=73 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=88 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
n=81 Participants
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) From Last Active Dose Taken to After a One-day Missed-dose
Change in msSBP
|
-0.50 mmHg
Standard Error 1.05
|
-1.28 mmHg
Standard Error 1.10
|
0.52 mmHg
Standard Error 1.06
|
3.27 mmHg
Standard Error 1.10
|
|
Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) From Last Active Dose Taken to After a One-day Missed-dose
Change in msDBP
|
0.76 mmHg
Standard Error 0.69
|
0.32 mmHg
Standard Error 0.79
|
-0.40 mmHg
Standard Error 0.78
|
0.97 mmHg
Standard Error 0.81
|
SECONDARY outcome
Timeframe: 8 weeks + 1 dayPopulation: All randomized patients except one patient from Aliskiren arm who was lost to follow up after visit 2.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Outcome measures
| Measure |
Ramipril
n=257 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
n=248 Participants
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III)
Patients with at least 1 AE
|
55 Participants
|
43 Participants
|
—
|
—
|
|
Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III)
Patients with at least 1 SAE
|
3 Participants
|
1 Participants
|
—
|
—
|
|
Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III)
Death
|
0 Participants
|
0 Participants
|
—
|
—
|
Adverse Events
Ramipril (Period II and III)
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo to Ramipril (Period III)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Aliskiren (Period II and III)
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo to Aliskiren (Period III)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ramipril (Period II and III)
n=257 participants at risk
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Ramipril (Period III)
n=118 participants at risk
In period III (double-blind withdrawal): At visit 4, part of the patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Aliskiren (Period II and III)
n=248 participants at risk
In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.
In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.
In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
Placebo to Aliskiren (Period III)
n=122 participants at risk
In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
normochromic normocytic anemia
|
0.00%
0/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.40%
1/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
spine metastasis
|
0.00%
0/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.40%
1/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Cardiac disorders
cardiac failure
|
0.00%
0/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.40%
1/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
bladder cancer
|
0.00%
0/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.40%
1/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
liver metastatis
|
0.00%
0/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.40%
1/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Gastrointestinal disorders
abdominal pain
|
0.39%
1/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
pancreatic adenocarcinoma
|
0.39%
1/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
0.39%
1/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
Cardiac disorders
atrial fibrillation
|
0.39%
1/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
|
General disorders
asthenia
|
0.39%
1/257 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/118 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/248 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
0.00%
0/122 • 8 weeks of period II + 1 day of Period III
The adverse events and serious adverse events are reported on randomized population except one patient who lost to follow up after visit 2.
|
Other adverse events
Adverse event data not reported
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER