Trial Outcomes & Findings for Efficacy of a Combination of Amlodipine/Valsartan on 24H Blood Pressure Control With One Nocturnal or Diurnal Intake a Day (NCT NCT00700271)

NCT ID: NCT00700271

Last Updated: 2011-05-19

Results Overview

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

478 participants

Primary outcome timeframe

Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Results posted on

2011-05-19

Participant Flow

Eligible patients entered a 4-week open-label amlodipine screening phase with amlodipine 5 mg taken orally once a day. At the end of the screening phase, patients whose blood pressure was not adequately controlled (defined as SBP/DBP \>= 125/80 mmHg 24-hr mean) on ambulatory blood pressure monitoring were randomized to one of two treatment groups.

Participant milestones

Participant milestones
Measure
Morning Intake
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Overall Study
STARTED
278
268
Overall Study
COMPLETED
264
256
Overall Study
NOT COMPLETED
14
12

Reasons for withdrawal

Reasons for withdrawal
Measure
Morning Intake
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Overall Study
Adverse Event
4
6
Overall Study
Protocol Violation
1
0
Overall Study
Administrative Reasons
1
0
Overall Study
Withdrawal by Subject
6
4
Overall Study
Lost to Follow-up
2
2

Baseline Characteristics

Efficacy of a Combination of Amlodipine/Valsartan on 24H Blood Pressure Control With One Nocturnal or Diurnal Intake a Day

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Total
n=479 Participants
Total of all reporting groups
Age Continuous
55.8 years
STANDARD_DEVIATION 9.89 • n=99 Participants
56.2 years
STANDARD_DEVIATION 9.59 • n=107 Participants
56.0 years
STANDARD_DEVIATION 9.74 • n=206 Participants
Sex: Female, Male
Female
114 Participants
n=99 Participants
111 Participants
n=107 Participants
225 Participants
n=206 Participants
Sex: Female, Male
Male
128 Participants
n=99 Participants
126 Participants
n=107 Participants
254 Participants
n=206 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Absolute Reduction From Baseline in 24-hour Mean Systolic Blood Pressure (SBP) on Ambulatory Blood Pressure Monitoring
-12.01 mmHg
Standard Error 0.70
-11.3 mmHg
Standard Error 0.71

SECONDARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Systolic Blood Pressure (SBP)
-13.50 mmHg
Standard Error 0.78
-11.99 mmHg
Standard Error 0.8
Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Diastolic Blood Pressure (DBP)
-7.56 mmHg
Standard Error 0.49
-7.11 mmHg
Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Systolic Blood Pressure (SBP)
-9.68 mmHg
Standard Error 0.74
-10.33 mmHg
Standard Error 0.76
Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Diastolic Blood Pressure (DBP)
-5.01 mmHg
Standard Error 0.46
-6.3 mmHg
Standard Error 0.47

SECONDARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Absolute Reduction From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
-6.53 mmHg
Standard Error 0.42
-6.79 mmHg
Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Systolic Blood Pressure (SBP)
-12.16 mmHg
Standard Error 0.88
-11.37 mmHg
Standard Error 0.90
Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring
Diastolic Blood Pressure (DBP)
-7.71 mmHg
Standard Error 0.59
-7.01 mmHg
Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for five minutes; the investigator then took three blood pressure and one pulse rate reading. The measurements were recorded at 1-2 minute intervals. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=231 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=232 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood Pressure
Systolic Blood Pressure (SBP)
-18.7 mmHg
Standard Error 0.9
-17.3 mmHg
Standard Error 0.9
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood Pressure
Diastolic Blood Pressure (DBP)
-10.1 mmHg
Standard Error 0.6
-8.6 mmHg
Standard Error 0.7

SECONDARY outcome

Timeframe: Screening visit (Week -4, prior to 4-week open-label screening phase) and Week 8 (after 8 weeks of combination therapy)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for five minutes; the investigator then took three blood pressure and one pulse rate reading. The measurements were recorded at 1-2 minute intervals. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Outcome measures

Outcome measures
Measure
Morning Intake
n=231 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=232 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood Pressure
Systolic Blood Pressure (SBP)
-32.2 mmHg
Standard Error 1.1
-29 mmHg
Standard Error 1.2
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood Pressure
Diastolic Blood Pressure (DBP)
-16.6 mmHg
Standard Error 0.8
-14.3 mmHg
Standard Error 0.8

SECONDARY outcome

Timeframe: Visit 4 (week 8)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Percentage of Participants With 24-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 125/80 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring
47.6 Percentage of Participants
46.9 Percentage of Participants

SECONDARY outcome

Timeframe: Visit 4 (week 8)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Percentage of Participants With Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 135/85 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring
65.3 Percentage of Participants
58.2 Percentage of Participants

SECONDARY outcome

Timeframe: Visit 4 (week 8)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Percentage of Participants With Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 120/70 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring
41.3 Percentage of participants
46.8 Percentage of participants

SECONDARY outcome

Timeframe: Visit 4 (week 8)

Population: The Intent-to-treat (ITT) population included all patients randomized and treated in the study and for whom two Ambulatory Blood Pressure Monitoring (ABPM) evaluations are available.

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for 5 minutes; the investigator then took 3 blood pressure and 1 pulse rate reading. The measurements were recorded at 1-2 minute intervals. BP Control is defined as msSBP/msDBP \<149/90 mmHg and/or \<130/80 mmHg if diabetes or renal insufficiency (RI).

Outcome measures

Outcome measures
Measure
Morning Intake
n=242 Participants
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=237 Participants
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Percentage of Participants With Controlled Office Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) at Endpoint
71.1 Percentage of participants
72.6 Percentage of participants

Adverse Events

Morning Intake

Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths

Evening Intake

Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Morning Intake
n=278 participants at risk
After randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening Intake
n=268 participants at risk
After randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Cardiac disorders
Atrial fibrillation
0.36%
1/278
0.00%
0/268
Cardiac disorders
Atrioventricular block
0.00%
0/278
0.37%
1/268
Cardiac disorders
Bradycardia
0.00%
0/278
0.37%
1/268
Cardiac disorders
Palpitations
0.36%
1/278
0.37%
1/268
Cardiac disorders
Sinus tachycardia
0.00%
0/278
0.37%
1/268
Metabolism and nutrition disorders
Hyperglycaemia
0.36%
1/278
0.00%
0/268
Nervous system disorders
Syncope
0.36%
1/278
0.00%
0/268
Psychiatric disorders
Stress
0.36%
1/278
0.00%
0/268
Renal and urinary disorders
Renal impairment
0.00%
0/278
0.37%
1/268

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; or publication of the trial results in their entirety.
  • Publication restrictions are in place

Restriction type: OTHER