Trial Outcomes & Findings for Valsartan/Amlodipine As Compared to Losartan Treatment in Stage 2 Systolic Hypertension (NCT NCT00931710)
NCT ID: NCT00931710
Last Updated: 2011-03-07
Results Overview
To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
488 participants
Primary outcome timeframe
Baseline to Week 6
Results posted on
2011-03-07
Participant Flow
Participant milestones
| Measure |
Valsartan/Amlodipine/HCTZ
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
241
|
247
|
|
Overall Study
COMPLETED
|
207
|
209
|
|
Overall Study
NOT COMPLETED
|
34
|
38
|
Reasons for withdrawal
| Measure |
Valsartan/Amlodipine/HCTZ
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Overall Study
Adverse Event
|
16
|
10
|
|
Overall Study
Abnormal test procedure results
|
2
|
0
|
|
Overall Study
Unsatisfactory therapeutic effects
|
5
|
12
|
|
Overall Study
Patient withdrew consent
|
4
|
9
|
|
Overall Study
Lost to Follow-up
|
6
|
5
|
|
Overall Study
Protocol deviation
|
1
|
2
|
Baseline Characteristics
Valsartan/Amlodipine As Compared to Losartan Treatment in Stage 2 Systolic Hypertension
Baseline characteristics by cohort
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
Total
n=488 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
55.0 years
STANDARD_DEVIATION 9.83 • n=5 Participants
|
57.1 years
STANDARD_DEVIATION 9.69 • n=7 Participants
|
56.1 years
STANDARD_DEVIATION 9.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
102 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
213 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
139 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
275 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 6Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure After 6 Weeks
Baseline
|
166.8 mmHg
Standard Deviation 7.03
|
168.5 mmHg
Standard Deviation 9.03
|
|
Change in Mean Sitting Systolic Blood Pressure After 6 Weeks
Week 6
|
135.5 mmHg
Standard Deviation 16.26
|
142.5 mmHg
Standard Deviation 18.89
|
|
Change in Mean Sitting Systolic Blood Pressure After 6 Weeks
Change from Baseline to Week 6
|
-31.3 mmHg
Standard Deviation 15.87
|
-26.0 mmHg
Standard Deviation 16.62
|
SECONDARY outcome
Timeframe: Baseline to Week 6Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks
Baseline
|
98.6 mmHg
Standard Deviation 7.71
|
97.6 mmHg
Standard Deviation 7.88
|
|
Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks
Week 6
|
85.1 mmHg
Standard Deviation 10.05
|
88.5 mmHg
Standard Deviation 11.36
|
|
Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks
Change from Baseline to Week 6
|
-13.6 mmHg
Standard Deviation 9.48
|
-9.1 mmHg
Standard Deviation 10.03
|
SECONDARY outcome
Timeframe: 3 and 6 weeksPopulation: Full Analysis Set (FAS).
To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP \< 140 mmHg and MSDBP \< 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Cumulative Percentage of Patients Achieving Blood Pressure Control
Week 3
|
30.5 cumulative percentage of patients
|
15.3 cumulative percentage of patients
|
|
Cumulative Percentage of Patients Achieving Blood Pressure Control
Week 6
|
61.5 cumulative percentage of patients
|
47.1 cumulative percentage of patients
|
SECONDARY outcome
Timeframe: 3 and 6 weeksPopulation: Full Analysis Set (FAS).
To compare the percentage of treatment responders (defined as patients with MSSBP \< 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Cumulative Percentage of Treatment Responders
Week 3
|
65.3 Cumulative percentage of responders
|
34.3 Cumulative percentage of responders
|
|
Cumulative Percentage of Treatment Responders
Week 6
|
87.0 Cumulative percentage of responders
|
71.5 Cumulative percentage of responders
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS). Last observation carried forward (LOCF).
To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Baseline MSSBP
|
166.8 mmHg
Standard Deviation 7.03
|
168.5 mmHg
Standard Deviation 9.03
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Week 12 MSSBP
|
130.8 mmHg
Standard Deviation 16.22
|
134.3 mmHg
Standard Deviation 19.41
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Change in MSSBP from baseline to Week 12
|
-36.0 mmHg
Standard Deviation 16.08
|
-34.2 mmHg
Standard Deviation 17.69
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Baseline MSDBP
|
98.6 mmHg
Standard Deviation 7.71
|
97.6 mmHg
Standard Deviation 7.88
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Week 12 MSDBP
|
82.5 mmHg
Standard Deviation 10.18
|
82.5 mmHg
Standard Deviation 11.43
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Change in MSDBP from baseline to Week 12
|
-16.1 mmHg
Standard Deviation 9.91
|
-15.1 mmHg
Standard Deviation 10.57
|
SECONDARY outcome
Timeframe: 3, 6, 9 and 12 weeksPopulation: Full Analysis Set (FAS).
To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension.
Outcome measures
| Measure |
Valsartan/Amlodipine/HCTZ
n=241 Participants
Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.
|
Losartan/HCTZ
n=247 Participants
Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
|
|---|---|---|
|
Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
Week 3
|
0.8 cumulative percentage of patients
|
0.8 cumulative percentage of patients
|
|
Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
Week 6
|
0.8 cumulative percentage of patients
|
0.8 cumulative percentage of patients
|
|
Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
Week 9
|
1.3 cumulative percentage of patients
|
0.8 cumulative percentage of patients
|
|
Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
Week 12
|
2.9 cumulative percentage of patients
|
4.5 cumulative percentage of patients
|
Adverse Events
Valsartan / Amlodipine / HCTZ
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Losartan / HCTZ
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valsartan / Amlodipine / HCTZ
n=241 participants at risk
Valsartan / amlodipine / HCTZ
|
Losartan / HCTZ
n=247 participants at risk
Losartan / HCTZ
|
|---|---|---|
|
General disorders
Non-cardiac chest pain
|
0.41%
1/241
|
0.00%
0/247
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/241
|
0.40%
1/247
|
|
Nervous system disorders
Dizziness
|
0.00%
0/241
|
0.40%
1/247
|
Other adverse events
| Measure |
Valsartan / Amlodipine / HCTZ
n=241 participants at risk
Valsartan / amlodipine / HCTZ
|
Losartan / HCTZ
n=247 participants at risk
Losartan / HCTZ
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
5.4%
13/241
|
3.2%
8/247
|
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