Trial Outcomes & Findings for Efficacy and Safety of Valsartan and Amlodipine (± HCTZ) in Adults With Moderate, Inadequately Controlled Hypertension (NCT NCT00523744)
NCT ID: NCT00523744
Last Updated: 2020-08-04
Results Overview
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
COMPLETED
PHASE3
257 participants
Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
2020-08-04
Participant Flow
Participant milestones
| Measure |
Amlodipine(AML)+Olmesartan, AML+Valsartan, AML+Valsartan+HCTZ
During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the Treatment Phase 2 participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg.
|
|---|---|
|
Phase 1 - Amlodipine+Olmesartan
STARTED
|
257
|
|
Phase 1 - Amlodipine+Olmesartan
COMPLETED
|
251
|
|
Phase 1 - Amlodipine+Olmesartan
NOT COMPLETED
|
6
|
|
Phase 2 - Amlodipine+Valsartan
STARTED
|
176
|
|
Phase 2 - Amlodipine+Valsartan
COMPLETED
|
173
|
|
Phase 2 - Amlodipine+Valsartan
NOT COMPLETED
|
3
|
|
Phase 3 - Amlodipine+Valsartan+HCTZ
STARTED
|
91
|
|
Phase 3 - Amlodipine+Valsartan+HCTZ
COMPLETED
|
91
|
|
Phase 3 - Amlodipine+Valsartan+HCTZ
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Amlodipine(AML)+Olmesartan, AML+Valsartan, AML+Valsartan+HCTZ
During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the Treatment Phase 2 participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg.
|
|---|---|
|
Phase 1 - Amlodipine+Olmesartan
Adverse Event
|
2
|
|
Phase 1 - Amlodipine+Olmesartan
Withdrawal by Subject
|
1
|
|
Phase 1 - Amlodipine+Olmesartan
Lost to Follow-up
|
2
|
|
Phase 1 - Amlodipine+Olmesartan
Administrative problems
|
1
|
|
Phase 2 - Amlodipine+Valsartan
Adverse Event
|
2
|
|
Phase 2 - Amlodipine+Valsartan
Lost to Follow-up
|
1
|
Baseline Characteristics
Efficacy and Safety of Valsartan and Amlodipine (± HCTZ) in Adults With Moderate, Inadequately Controlled Hypertension
Baseline characteristics by cohort
| Measure |
Amlodipine(AML)+Olmesartan, AML+Valsartan, AML+Valsartan+HCTZ
n=257 Participants
During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the Treatment Phase 2 participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg.
|
|---|---|
|
Age, Continuous
Phase 1 - Amlodipine+olmesartan
|
58.8 years
STANDARD_DEVIATION 12.38 • n=39 Participants
|
|
Age, Continuous
Phase 2 - Amlodipine+valsartan
|
59.8 years
STANDARD_DEVIATION 11.84 • n=39 Participants
|
|
Age, Continuous
Phase 3 - Amlodipine+valsartan+HCTZ
|
60.9 years
STANDARD_DEVIATION 10.98 • n=39 Participants
|
|
Sex/Gender, Customized
Phase 1 - Amlodipine+olmesartan - Female
|
112 participants
n=39 Participants
|
|
Sex/Gender, Customized
Phase 1 - Amlodipine+olmesartan - Male
|
145 participants
n=39 Participants
|
|
Sex/Gender, Customized
Phase 2 - Amlodipine+valsartan - Female
|
76 participants
n=39 Participants
|
|
Sex/Gender, Customized
Phase 2 - Amlodipine+valsartan - Male
|
100 participants
n=39 Participants
|
|
Sex/Gender, Customized
Phase 3 - Amlodipine+valsartan+HCTZ - Female
|
32 participants
n=39 Participants
|
|
Sex/Gender, Customized
Phase 3 - Amlodipine+valsartan+HCTZ - Male
|
59 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study
|
-9.13 mmHg
95% Confidence Interval 1.97 • Interval -10.19 to -8.06
|
PRIMARY outcome
Timeframe: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study
|
-5.22 mmHg
Interval -6.76 to -3.68
|
SECONDARY outcome
Timeframe: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study
|
-7.87 mmHg
95% Confidence Interval 9.48 • Interval -9.33 to -6.11
|
SECONDARY outcome
Timeframe: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Sitting Pulse Pressure During the Core Phase of the Study
|
1.26 mmHg
95% Confidence Interval 9.64 • Interval 0.49 to 3.01
|
SECONDARY outcome
Timeframe: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Sitting Pulse Rate During the Core Phase of the Study
|
-1.93 BPM (beats per minute)
Interval -3.06 to -0.79
|
SECONDARY outcome
Timeframe: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study
msSBP < 140 mmHg
|
44.6 Percentage of participants
|
|
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study
msDBP < 90 mmHg
|
72.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline of Phase 2 (Week 4) to end of Phase 2 (Week 8)Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 (Week 8) compared to Baseline in Phase 2 (week 4) or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=175 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study
msSBP response
|
47.4 Percentage of participants
|
|
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study
msDBP response
|
73.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study
|
-10.84 mmHg
Interval -12.94 to -8.75
|
SECONDARY outcome
Timeframe: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Sitting Pulse Pressure During the Extension Phase of the Study
|
-5.62 mmHg
Interval -7.74 to -3.5
|
SECONDARY outcome
Timeframe: Baseline Phase 3 (Week 8) to end of Phase 3 (week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Change in Sitting Pulse Rate During the Extension Phase of the Study
|
0.09 BPM (beats per minute)
Interval -1.36 to 1.54
|
SECONDARY outcome
Timeframe: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study
msSBP < 140 mmHg
|
59.3 Percentage of participants
|
|
Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study
msDBP < 90 mmHg
|
83.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline of Phase 3 (Week 8) to end of Phase 3 (Week 12)Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 3 compared to Baseline in Phase 3 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 3 compared to Baseline in Phase 3.
Outcome measures
| Measure |
Amlodipine+Valsartan - Phase 2
n=91 Participants
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
|---|---|
|
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study
msSBP response
|
61.5 Percentage of participants
|
|
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study
msDBP response
|
83.5 Percentage of participants
|
Adverse Events
Phase 1 - Amlodipine+Olmesartan
Phase 2 - Amlodipine+Valsartan
Phase 3 - Amlodipine+Valsartan+HCTZ
Serious adverse events
| Measure |
Phase 1 - Amlodipine+Olmesartan
n=257 participants at risk
4 weeks treatment with amlodipine 10 mg plus olmesartan 20 mg taken orally once daily in the morning.
|
Phase 2 - Amlodipine+Valsartan
n=176 participants at risk
Patients with uncontrolled mean sitting diastolic BP (msDBP ≥ 90 mmHg) at the end of Phase 1 were treated for 4 weeks with amlodipine 10 mg plus valsartan 160 mg taken orally in the morning.
|
Phase 3 - Amlodipine+Valsartan+HCTZ
n=91 participants at risk
Patients with uncontrolled mean sitting systolic or diastolic blood pressure (msDBP ≥ 90 mmHg and/or msSBP ≥ 140 mmHg) at the end of Phase 2 were offered a 4 week treatment extension with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg taken orally in the morning.
|
|---|---|---|---|
|
Ear and labyrinth disorders
SUDDEN HEARING LOSS
|
0.39%
1/257
|
0.00%
0/176
|
0.00%
0/91
|
Other adverse events
Adverse event data not reported
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