Trial Outcomes & Findings for 8 Weeks Study to Evaluate the Efficacy and Safety of Valsartan in Combination With Aliskiren Compared to Valsartan Alone in Patients With Stage 2 Hypertension (NCT NCT00809926)
NCT ID: NCT00809926
Last Updated: 2011-05-02
Results Overview
To compare the change from baseline in MSSBP after 8 weeks of treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
COMPLETED
PHASE4
451 participants
Baseline to Week 8
2011-05-02
Participant Flow
Participant milestones
| Measure |
Valsartan/Aliskiren
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Overall Study
STARTED
|
232
|
219
|
|
Overall Study
COMPLETED
|
201
|
196
|
|
Overall Study
NOT COMPLETED
|
31
|
23
|
Reasons for withdrawal
| Measure |
Valsartan/Aliskiren
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Overall Study
Adverse Event
|
18
|
10
|
|
Overall Study
Unsatisfactory therapeutic effect
|
3
|
3
|
|
Overall Study
Patient withdrew consent
|
8
|
6
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Administrative Problems
|
0
|
1
|
|
Overall Study
Protocol deviation
|
0
|
2
|
Baseline Characteristics
8 Weeks Study to Evaluate the Efficacy and Safety of Valsartan in Combination With Aliskiren Compared to Valsartan Alone in Patients With Stage 2 Hypertension
Baseline characteristics by cohort
| Measure |
Valsartan/Aliskiren
n=232 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=219 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
Total
n=451 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
57.5 years
STANDARD_DEVIATION 11.1 • n=99 Participants
|
56.7 years
STANDARD_DEVIATION 11.0 • n=107 Participants
|
57.1 years
STANDARD_DEVIATION 11.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
107 Participants
n=99 Participants
|
116 Participants
n=107 Participants
|
223 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
125 Participants
n=99 Participants
|
103 Participants
n=107 Participants
|
228 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 8Population: Intent-to-treat (ITT) population consisted of all randomized patients who received at least 1 dose of study drug and had valid baseline and 1 valid post-baseline assessment of an efficacy variable. The last-observation-carried-forward (LOCF) method was used for replacing the missing values of the post-baseline assessments for ITT analysis at wk 8.
To compare the change from baseline in MSSBP after 8 weeks of treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
Baseline
|
164.8 mm Hg
Standard Deviation 4.54
|
166.2 mm Hg
Standard Deviation 5.23
|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
Week 8
|
142.3 mm Hg
Standard Deviation 17.01
|
145.6 mm Hg
Standard Deviation 17.55
|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8
Change from Baseline to Week 8
|
-22.5 mm Hg
Standard Deviation 16.04
|
-20.6 mm Hg
Standard Deviation 16.25
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: Intent-to-treat (ITT) population consisted of all randomized patients who received at least 1 dose of study drug and had valid baseline and 1 valid post-baseline assessment of an efficacy variable. The last-observation-carried-forward (LOCF) method was used for replacing the missing values of the post-baseline assessments for ITT analysis at wk 8.
To compare the change in MSDBP after 8 weeks of treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan (160 mg, 320 mg) treatment regimen in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
Baseline
|
93.9 mm Hg
Standard Deviation 8.22
|
94.8 mm Hg
Standard Deviation 8.68
|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
Week 8
|
85.7 mm Hg
Standard Deviation 10.94
|
86.4 mm Hg
Standard Deviation 10.34
|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8
Change from Baseline to Week 8
|
-8.2 mm Hg
Standard Deviation 9.77
|
-8.3 mm Hg
Standard Deviation 9.49
|
SECONDARY outcome
Timeframe: At Week 8Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had valid baseline and at least one valid post-baseline assessment of an efficacy variable.
To evaluate the percentage of patients achieving blood pressure control (defined as patients achieving a MSSBP \<140 mmHg and MSDBP \<90 mmHg) at week 8 following treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Percentage of Patients Achieving Blood Pressure Control (Defined as Patients Achieving a MSSBP <140 mmHg and MSDBP <90 mmHg) at Week 8
|
44.3 percentage of patients
|
36.2 percentage of patients
|
SECONDARY outcome
Timeframe: At Week 8Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had valid baseline and at least one valid post-baseline assessment of an efficacy variable.
To compare the percentage of responders (defined as patients with MSSBP \<140 mmHg or a decrease from baseline ≥20 mmHg) at week 8 following treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Percentage of Responders (Defined as Patients With MSSBP <140 mmHg or a Decrease From Baseline ≥20 mmHg) at Week 8
|
64.7 percentage of responders
|
53.1 percentage of responders
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had valid baseline and at least one valid post-baseline assessment of an efficacy variable.
To assess the change from baseline in PRA after 8 weeks of treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Mean Change From Baseline in Plasma Renin Activity (PRA) at Week 8
Baseline
|
0.992 ng/mL/h
Standard Deviation 1.290
|
0.831 ng/mL/h
Standard Deviation 0.854
|
|
Mean Change From Baseline in Plasma Renin Activity (PRA) at Week 8
Week 8
|
0.436 ng/mL/h
Standard Deviation 0.659
|
2.450 ng/mL/h
Standard Deviation 3.73
|
|
Mean Change From Baseline in Plasma Renin Activity (PRA) at Week 8
Change from Baseline to Week 8
|
-0.540 ng/mL/h
Standard Deviation 1.285
|
1.577 ng/mL/h
Standard Deviation 3.528
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had valid baseline and at least one valid post-baseline assessment of an efficacy variable.
To assess the change from baseline in PRC after 8 weeks of treatment with a valsartan and aliskiren treatment regimen (160/150 mg, 320/300 mg) versus a valsartan treatment regimen (160 mg, 320 mg) in patients with Stage 2 Hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Mean Change From Baseline in Plasma Renin Concentration (PRC) at Week 8
Baseline
|
8.286 ng/L
Standard Deviation 10.893
|
8.065 ng/L
Standard Deviation 14.932
|
|
Mean Change From Baseline in Plasma Renin Concentration (PRC) at Week 8
Week 8
|
142.833 ng/L
Standard Deviation 293.228
|
20.089 ng/L
Standard Deviation 31.771
|
|
Mean Change From Baseline in Plasma Renin Concentration (PRC) at Week 8
Change from Baseline to Week 8
|
135.515 ng/L
Standard Deviation 296.758
|
11.988 ng/L
Standard Deviation 32.679
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to week 8Population: The analysis included ITT patients who completed the double-blind treatment period \[those patients with a final observation at week 8, also known as observed cases (OC)\]. This analysis differed from the ITT-LOCF analysis, in that it did not include patients who discontinued from the trial prematurely.
To evaluate the change from baseline in MSSBP (mmHg) at Week 8; primary efficacy variable at primary time point in ITT population - patients who completed the double-blind treatment period.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=201 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=196 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Completers Analysis for Change From Baseline in MSSBP at Week 8
Baseline
|
164.8 mm Hg
Standard Deviation 4.54
|
166.2 mm Hg
Standard Deviation 5.23
|
|
Completers Analysis for Change From Baseline in MSSBP at Week 8
Week 8
|
140.9 mm Hg
Standard Deviation 15.74
|
145.9 mm Hg
Standard Deviation 16.89
|
|
Completers Analysis for Change From Baseline in MSSBP at Week 8
Change from Baseline to Week 8
|
-24.0 mm Hg
Standard Deviation 14.70
|
-20.3 mm Hg
Standard Deviation 15.49
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through week 8Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had valid baseline and at least one valid post-baseline assessment of an efficacy variable.
To evaluate the change from baseline in MSSBP (mmHg) after 8 weeks; primary efficacy variable (ITT population) using Longitudinal analysis (A repeated measures analysis where assessments over time are considered , as opposed to looking at a single point in time.)
Outcome measures
| Measure |
Valsartan/Aliskiren
n=230 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=217 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Longitudinal Repeated Measure Analysis for Change in MSSBP From Baseline Through Week 8
|
-23.2 mm Hg
Standard Error 1.04
|
-20.1 mm Hg
Standard Error 1.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to week 8Population: Patients who were willing to participate in the Ambulatory Blood Pressure Monitoring (ABPM) substudy and who met the study inclusion and exclusion criteria for randomization.
To evaluate 24-hour ambulatory systolic blood pressure measurements in a subset of patients after 8 weeks of treatment with the combination of valsartan and aliskiren versus valsartan monotherapy in patients with stage 2 hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=58 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=53 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (MASBP).
Baseline
|
146.1 mm Hg
Standard Deviation 9.14
|
143.5 mm Hg
Standard Deviation 14.10
|
|
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (MASBP).
Week 8
|
130.3 mm Hg
Standard Deviation 13.41
|
137.6 mm Hg
Standard Deviation 17.11
|
|
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (MASBP).
Change from Baseline to Week 8
|
-15.8 mm Hg
Standard Deviation 11.42
|
-6.0 mm Hg
Standard Deviation 13.34
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to week 8Population: Patients who were willing to participate in the ABPM substudy and who met the study inclusion and exclusion criteria for randomization.
To evaluate 24-hour ambulatory diastolic blood pressure measurements in a subset of patients after 8 weeks of treatment with the combination of valsartan and aliskiren versus valsartan monotherapy in patients with stage 2 hypertension.
Outcome measures
| Measure |
Valsartan/Aliskiren
n=58 Participants
For the first 2 weeks patients received Valsartan/aliskiren (160/150mg). For the remaining 6 weeks, all patients received Valsartan/aliskiren 320/300mg (forced titration).
|
Valsartan
n=53 Participants
For the first 2 weeks patients received Valsartan 160 mg. For the remaining 6 weeks, all patients received Valsartan 320 mg (forced titration).
|
|---|---|---|
|
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (MADBP)
Baseline
|
87.9 mm Hg
Standard Deviation 7.28
|
85.7 mm Hg
Standard Deviation 9.26
|
|
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (MADBP)
Week 8
|
78.2 mm Hg
Standard Deviation 9.44
|
81.7 mm Hg
Standard Deviation 10.11
|
|
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (MADBP)
Change from Baseline to Week 8
|
-9.7 mm Hg
Standard Deviation 7.02
|
-4.0 mm Hg
Standard Deviation 8.09
|
Adverse Events
Valsartan/ Aliskiren
Valsartan
Serious adverse events
| Measure |
Valsartan/ Aliskiren
n=232 participants at risk
Valsartan/aliskiren (160/150mg) for 2 weeks followed by forced titration to valsartan/aliskiren (320/300mg) for the remaining 6 weeks
|
Valsartan
n=219 participants at risk
Valsartan (160mg) for 2weeks followed by forced titration toValsartan (320mg) for the remaining 6 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphocytosis
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Cardiac disorders
Palpitations
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Gastrointestinal disorders
Diarrhoea
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Gastrointestinal disorders
Vomiting
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
General disorders
Chest discomfort
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
General disorders
Non-cardiac chest pain
|
0.86%
2/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Infections and infestations
Gastroenteritis
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Metabolism and nutrition disorders
Dehydration
|
0.86%
2/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.43%
1/232 • Baseline through week 8
|
0.00%
0/219 • Baseline through week 8
|
|
Nervous system disorders
Anaesthesia
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Psychiatric disorders
Conversion disorder
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/232 • Baseline through week 8
|
0.46%
1/219 • Baseline through week 8
|
Other adverse events
| Measure |
Valsartan/ Aliskiren
n=232 participants at risk
Valsartan/aliskiren (160/150mg) for 2 weeks followed by forced titration to valsartan/aliskiren (320/300mg) for the remaining 6 weeks
|
Valsartan
n=219 participants at risk
Valsartan (160mg) for 2weeks followed by forced titration toValsartan (320mg) for the remaining 6 weeks
|
|---|---|---|
|
Nervous system disorders
Headache
|
6.0%
14/232 • Baseline through week 8
|
6.8%
15/219 • Baseline through week 8
|
Additional Information
Study Director
Novartis Pharmaceuticals
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