Trial Outcomes & Findings for Effect of the Fixed Dose Combination Amlodipine/Valsartan on Central Aortic Blood Pressure in Uncontrolled Essential Hypertension With Amlodipine 5 mg (NCT NCT00687973)

NCT ID: NCT00687973

Last Updated: 2011-03-11

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 393 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2011-03-11

Participant Flow

Participant milestones

Measure	Valsartan/Amlodipine 160/10 mg Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Overall Study STARTED	193	200
Overall Study COMPLETED	169	162
Overall Study NOT COMPLETED	24	38

Reasons for withdrawal

Measure	Valsartan/Amlodipine 160/10 mg Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Overall Study Adverse Event	18	28
Overall Study Lack of Efficacy	2	3
Overall Study Protocol Violation	1	2
Overall Study Administrative Reasons	0	2
Overall Study Withdrawal by Subject	3	3

Baseline Characteristics

Effect of the Fixed Dose Combination Amlodipine/Valsartan on Central Aortic Blood Pressure in Uncontrolled Essential Hypertension With Amlodipine 5 mg

Baseline characteristics by cohort

Measure	Valsartan/Amlodipine 160/10 mg n=193 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=200 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Total n=393 Participants Total of all reporting groups
Age Continuous	57.5 years STANDARD_DEVIATION 9.94 • n=93 Participants	56.2 years STANDARD_DEVIATION 11.09 • n=4 Participants	56.9 years STANDARD_DEVIATION 10.55 • n=27 Participants
Sex: Female, Male Female	82 Participants n=93 Participants	101 Participants n=4 Participants	183 Participants n=27 Participants
Sex: Female, Male Male	111 Participants n=93 Participants	99 Participants n=4 Participants	210 Participants n=27 Participants
Region of Enrollment France	193 participants n=93 Participants	200 participants n=4 Participants	393 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=176 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=178 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 24 (Radial Measurement)	-13.65 mmHg Standard Error 1.15	-9.7 mmHg Standard Error 1.09

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=183 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=189 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Central Systolic Blood Pressure (SBP) at Week 8 (Radial Measurement)	-10.92 mmHg Standard Error 1.18	-8.3 mmHg Standard Error 1.12

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=176 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=178 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Central Pulse Pressure at Week 24 (Radial Measurement)	-5.5 mmHg Standard Error 0.65	-1.7 mmHg Standard Error 0.63

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

To calculate the blood pressure augmentation index, the inflection point of the pressure curve corresponding to the return of the reflection wave was determined. The ratio between the pressure located above and below the inflection point was calculated.

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=181 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=187 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Augmentation Index (Aix) at Week 8	-2.21 Ratio Standard Error 0.78	3.61 Ratio Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=175 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=178 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Aix at Week 24	-4.10 Ratio Standard Error 0.72	2.40 Ratio Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

The heart rate correction was computed by a multivariate model analysis

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=169 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=170 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Aix Corrected to Heart Rate at Week 24	-4.12 Ratio Standard Error 0.67	-2.43 Ratio Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent to treat (ITT) population; Last Observation Carried Forward (LOCF)

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=139 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=147 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Pulse Wave Velocity at Week 24 (Radial Measurement)	-0.98 m/s Standard Error 0.18	-0.95 m/s Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population

Applanation tonometry is a measurement of aortic pressure and vascular stiffness. To assess the central aortic blood pressure, it is necessary to calibrate the applanation tonometry device using the brachial blood pressure.

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=176 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=176 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) SBP	-12.93 mmHg Standard Error 1.14	-11.78 mmHg Standard Error 1.11
Change From Baseline of Brachial SBP/DBP at Week 24 (Tonometry Center) DBP	-7.85 mmHg Standard Error 0.70	-7.94 mmHg Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=176 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=176 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Brachial Pulse Pressure at Week 24 (Tonometry Center)	-5.02 mmHg Standard Error 0.72	-3.66 mmHg Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=183 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=185 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of SBP/DBP at Week 24 (Office BP) SBP	-14.49 mmHg Standard Error 1.08	-16.94 mmHg Standard Error 1.07
Change From Baseline of SBP/DBP at Week 24 (Office BP) DBP	-8.17 mmHg Standard Error 0.72	-10.45 mmHg Standard Error 0.71

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

Outcome measures

Measure	Valsartan/Amlodipine 160/10 mg n=183 Participants Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=185 Participants Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Change From Baseline of Pulse Pressure at Week 24 (Office BP)	-6.32 mmHg Standard Deviation 0.81	-6.48 mmHg Standard Deviation 0.81

Adverse Events

Amlodipine 5 mg

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Valsartan/Amlodipine 160/10 mg

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Atenolol/Amlodipine 100/10 mg

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Amlodipine 5 mg n=393 participants at risk Run-in: Amlodipine 5 mg	Valsartan/Amlodipine 160/10 mg n=193 participants at risk Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=200 participants at risk Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/393	0.52% 1/193	0.00% 0/200
Hepatobiliary disorders Cholecystitis	0.25% 1/393	0.00% 0/193	0.00% 0/200
Injury, poisoning and procedural complications Head injury	0.00% 0/393	0.00% 0/193	0.50% 1/200
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	0.00% 0/393	0.52% 1/193	0.00% 0/200
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/393	0.00% 0/193	0.50% 1/200
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/393	0.00% 0/193	0.50% 1/200
Psychiatric disorders Suicide attempt	0.00% 0/393	0.00% 0/193	0.50% 1/200
Renal and urinary disorders Renal colic	0.25% 1/393	0.00% 0/193	0.00% 0/200
Renal and urinary disorders Renal failure	0.25% 1/393	0.00% 0/193	0.00% 0/200
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/393	0.52% 1/193	0.00% 0/200
Surgical and medical procedures Cholecystectomy	0.25% 1/393	0.00% 0/193	0.00% 0/200
Surgical and medical procedures Cyst removal	0.00% 0/393	0.52% 1/193	0.00% 0/200
Surgical and medical procedures Inguinal hernia repair	0.00% 0/393	0.00% 0/193	0.50% 1/200
Surgical and medical procedures Joint arthroplasty	0.00% 0/393	0.52% 1/193	0.00% 0/200

Other adverse events

Measure	Amlodipine 5 mg n=393 participants at risk Run-in: Amlodipine 5 mg	Valsartan/Amlodipine 160/10 mg n=193 participants at risk Patients were treated with valsartan/amlodipine 80/5 mg for 8 weeks followed by forced uptitration to valsartan/amlodipine 160/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.	Atenolol/Amlodipine 100/10 mg n=200 participants at risk Patients were treated with atenolol/amlodipine 50/5 mg for 8 weeks followed by forced uptitration to atenolol/amlodipine 100/10 mg for 16 weeks. All doses were taken orally once daily in the morning, except on days when clinic visits were scheduled.
General disorders Oedema peripheral	2.5% 10/393	15.5% 30/193	15.5% 31/200

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