Trial Outcomes & Findings for Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension (NCT NCT00413049)

NCT ID: NCT00413049

Last Updated: 2011-04-29

Results Overview

Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 698 participants
• Primary outcome timeframe: Baseline to end of study (Week 8)
• Results posted on: 2011-04-29

Participant Flow

Two patients in the valsartan/amlodipine group were excluded from the intent-to-treat population used for the efficacy analyses for having no post-baseline efficacy assessment.

Participant milestones

Measure	Valsartan/Amlodipine 80/5 mg 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Study STARTED	349	349
Overall Study COMPLETED	325	331
Overall Study NOT COMPLETED	24	18

Reasons for withdrawal

Measure	Valsartan/Amlodipine 80/5 mg 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Study Protocol Violation	3	1
Overall Study Subject no longer requires study drug	0	1
Overall Study Adverse Event	10	8
Overall Study Withdrawal by Subject	7	5
Overall Study Lost to Follow-up	2	3
Overall Study Abnormal laboratory value(s)	1	0
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension

Baseline characteristics by cohort

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Total n=696 Participants Total of all reporting groups
Age Continuous	53.4 years STANDARD_DEVIATION 9.7 • n=5 Participants	54.2 years STANDARD_DEVIATION 9.1 • n=7 Participants	53.8 years STANDARD_DEVIATION 9.4 • n=5 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	109 Participants n=7 Participants	243 Participants n=5 Participants
Sex: Female, Male Male	213 Participants n=5 Participants	240 Participants n=7 Participants	453 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to end of study (Week 8)

Population: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)	-9.7 mmHg Standard Error 0.42	-7.1 mmHg Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline to end of study (Week 8)

Population: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)	-11.4 mmHg Standard Error 0.61	-7.4 mmHg Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline to end of study (Week 8)

Population: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

A patient achieved a diastolic response if their msDBP < 90 mmHg at Week 8 or they had a ≥ 10 mmHg decrease in msDBP compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8)	79.3 Percentage of patients	66.8 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to end of study (Week 8)

Population: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

A patient achieved diastolic control if their msDBP < 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8)	75.5 Percentage of patients	64.5 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to end of study (Week 8)

Population: Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

A patient achieved overall control if the msSBP/msDBP < 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=347 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Percentage of Patients Achieving Overall Control at the End of the Study (Week 8)	69.2 Percentage of patients	57.6 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to end of study (Week 8)

Two 24 hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline prior to randomization and one at Week 8 (end of study), in a subset of the intent-to-treat population of patients. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. A correlation was made between the ABPM device readings and measurements taken with a mercury sphygmomanometer and stethoscope. Following the correlation procedure, BP was measured at study specified intervals. A negative change score indicates lowered BP.

Outcome measures

Measure	Valsartan/Amlodipine 80/5 mg n=41 Participants 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=41 Participants 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8) Systolic BP	-7.3 mmHg Standard Deviation 7.62	-0.2 mmHg Standard Deviation 8.64
Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8) Diastolic BP	-6.3 mmHg Standard Deviation 5.85	0.3 mmHg Standard Deviation 5.82

Adverse Events

Valsartan/Amlodipine 80/5 mg

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Amlodipine 5 mg

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Valsartan/Amlodipine 80/5 mg n=349 participants at risk 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Amlodipine 5 mg n=349 participants at risk 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Gastrointestinal disorders Gastric ulcer	0.29% 1/349	0.29% 1/349
Injury, poisoning and procedural complications Humerus fracture	0.29% 1/349	0.00% 0/349
Musculoskeletal and connective tissue disorders Jaw cyst	0.29% 1/349	0.00% 0/349
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/349	0.29% 1/349
Nervous system disorders Post herpetic neuralgia	0.29% 1/349	0.00% 0/349

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER