Trial Outcomes & Findings for Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension (NCT NCT00437645)
NCT ID: NCT00437645
Last Updated: 2014-11-11
Results Overview
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1183 participants
Primary outcome timeframe
Baseline to Week 8
Results posted on
2014-11-11
Participant Flow
Participant milestones
| Measure |
Valsartan/Amlodipine 160/5 mg
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Overall Study
STARTED
|
592
|
591
|
|
Overall Study
COMPLETED
|
557
|
476
|
|
Overall Study
NOT COMPLETED
|
35
|
115
|
Reasons for withdrawal
| Measure |
Valsartan/Amlodipine 160/5 mg
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
84
|
|
Overall Study
Withdrawal by Subject
|
10
|
22
|
|
Overall Study
Protocol Violation
|
3
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
|
Overall Study
Administrative problems
|
2
|
1
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
|
Overall Study
Condition no longer requires study drug
|
1
|
1
|
Baseline Characteristics
Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
Baseline characteristics by cohort
| Measure |
Valsartan/Amlodipine 160/5 mg
n=592 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=591 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Total
n=1183 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Overall study
|
65.6 Age (years)
STANDARD_DEVIATION 7.56 • n=5 Participants
|
65.4 Age (years)
STANDARD_DEVIATION 7.16 • n=7 Participants
|
65.5 Age (years)
STANDARD_DEVIATION 7.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
285 Participants
n=5 Participants
|
284 Participants
n=7 Participants
|
569 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
307 Participants
n=5 Participants
|
307 Participants
n=7 Participants
|
614 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 8Population: Intent-to-treat (ITT) population: All randomized patients who had a baseline and at least one post-baseline efficacy assessment. For patients who discontinued prior to Week 8, the last post-baseline msSBP measurement collected was used for the analysis (last observation carried forward \[LOCF\]).
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Outcome measures
| Measure |
Valsartan/Amlodipine 160/5 mg
n=567 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=510 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
|
-8.01 mmHg
Standard Error 0.5944
|
-6.30 mmHg
Standard Error 0.6088
|
PRIMARY outcome
Timeframe: Baseline to Week 8Population: Safety population: All randomized patients.
Only occurrences of peripheral edema quantified as a reported adverse event coded as peripheral edema were included in the analysis. If a patient experienced more than one occurrence of peripheral edema between Day 1 and Week 8, it was only counted once in the analysis.
Outcome measures
| Measure |
Valsartan/Amlodipine 160/5 mg
n=592 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=591 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Percentage of Patients With Peripheral Edema From Baseline to Week 8
|
6.6 Percentage of patients
|
31.1 Percentage of patients
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: Intent-to-treat (ITT) population: All randomized patients who had a baseline and at least one post-baseline efficacy assessment. For patients who discontinued prior to Week 8, the last post-baseline msSBP measurement collected was used for the analysis (last observation carried forward \[LOCF\]).
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Outcome measures
| Measure |
Valsartan/Amlodipine 160/5 mg
n=567 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=510 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
|
-4.65 mmHg
Standard Error 0.3616
|
-4.13 mmHg
Standard Error 0.3690
|
SECONDARY outcome
Timeframe: Baseline to Weeks 4, 8, and 12Population: Intent-to-treat (ITT) population: All randomized patients who had a baseline and at least one post-baseline efficacy assessment. For patients who discontinued prior to Week 8, the last post-baseline msSBP measurement collected was used for the analysis (last observation carried forward \[LOCF\]).
Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Outcome measures
| Measure |
Valsartan/Amlodipine 160/5 mg
n=576 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=535 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msDBP: Week 8 (n=576, 510)
|
-4.68 mmHg
Standard Error 0.3632
|
-3.97 mmHg
Standard Error 0.3736
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msDBP: Week 12 (n=569, 531)
|
-5.50 mmHg
Standard Error 0.03735
|
-4.90 mmHg
Standard Error 0.3785
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msSBP: Week 4 (n=576, 535)
|
-8.40 mmHg
Standard Error 0.5559
|
-6.48 mmHg
Standard Error 0.5676
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msSBP: Week 8 (n=567, 510)
|
-8.15 mmHg
Standard Error 0.6065
|
-6.11 mmHg
Standard Error 0.6266
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msSBP: Week 12 (n=569, 531)
|
-9.08 mmHg
Standard Error 0.6968
|
-7.82 mmHg
Standard Error 0.7088
|
|
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
msDBP: Week 4 (n=576, 535)
|
-5.05 mmHg
Standard Error 0.3559
|
-4.23 mmHg
Standard Error 0.3623
|
SECONDARY outcome
Timeframe: Baseline to Weeks 4, 8, and 12Population: Intent-to-treat (ITT) population: All randomized patients who had a baseline and at least one post-baseline efficacy assessment. For patients who discontinued prior to Week 8, the last post-baseline msSBP measurement collected was used for the analysis (last observation carried forward \[LOCF\]).
Systolic response was defined as msSBP \< 130 mmHg or at least a 20 mmHg reduction from baseline in msSBP at Weeks 4, 8, and 12. Blood pressure (BP) was measured at trough (24±3 hours post-dose). 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 with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated.
Outcome measures
| Measure |
Valsartan/Amlodipine 160/5 mg
n=576 Participants
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=535 Participants
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
Week 4 (n=576, 535)
|
35.07 Percentage of patients
|
25.42 Percentage of patients
|
|
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
Week 8 (n=567, 510)
|
34.22 Percentage of patients
|
25.49 Percentage of patients
|
|
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
Week 12 (n=569, 531)
|
37.96 Percentage of patients
|
31.26 Percentage of patients
|
Adverse Events
Valsartan/Amlodipine 160/5 mg
Serious events: 11 serious events
Other events: 61 other events
Deaths: 0 deaths
Amlodipine 10 mg
Serious events: 8 serious events
Other events: 201 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valsartan/Amlodipine 160/5 mg
n=592 participants at risk
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=591 participants at risk
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.17%
1/592
|
0.00%
0/591
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/592
|
0.17%
1/591
|
|
Gastrointestinal disorders
Gastrointestinal necrosis
|
0.00%
0/592
|
0.17%
1/591
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/592
|
0.17%
1/591
|
|
General disorders
Asthenia
|
0.17%
1/592
|
0.00%
0/591
|
|
General disorders
Pyrexia
|
0.17%
1/592
|
0.00%
0/591
|
|
Hepatobiliary disorders
Cholecystitis
|
0.34%
2/592
|
0.00%
0/591
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.17%
1/592
|
0.00%
0/591
|
|
Infections and infestations
Hantavirus pulmonary infection
|
0.17%
1/592
|
0.00%
0/591
|
|
Infections and infestations
Urinary tract infection
|
0.17%
1/592
|
0.00%
0/591
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.17%
1/592
|
0.00%
0/591
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/592
|
0.17%
1/591
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.17%
1/592
|
0.00%
0/591
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.17%
1/592
|
0.00%
0/591
|
|
Investigations
Blood creatine phosphokinase increased
|
0.17%
1/592
|
0.00%
0/591
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.17%
1/592
|
0.00%
0/591
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.17%
1/592
|
0.00%
0/591
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/592
|
0.17%
1/591
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.17%
1/592
|
0.00%
0/591
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.17%
1/592
|
0.00%
0/591
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/592
|
0.17%
1/591
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/592
|
0.17%
1/591
|
|
Nervous system disorders
Dysphasia
|
0.00%
0/592
|
0.17%
1/591
|
|
Psychiatric disorders
Neglect of personal appearance
|
0.00%
0/592
|
0.17%
1/591
|
|
Renal and urinary disorders
Bladder tamponade
|
0.17%
1/592
|
0.00%
0/591
|
|
Renal and urinary disorders
Haematuria
|
0.17%
1/592
|
0.00%
0/591
|
|
Renal and urinary disorders
Renal impairment
|
0.17%
1/592
|
0.00%
0/591
|
|
Reproductive system and breast disorders
Epididymitis
|
0.00%
0/592
|
0.17%
1/591
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/592
|
0.17%
1/591
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/592
|
0.17%
1/591
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/592
|
0.17%
1/591
|
Other adverse events
| Measure |
Valsartan/Amlodipine 160/5 mg
n=592 participants at risk
Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
Amlodipine 10 mg
n=591 participants at risk
Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.
|
|---|---|---|
|
General disorders
Oedema peripheral
|
7.3%
43/592
|
31.5%
186/591
|
|
Nervous system disorders
Headache
|
3.0%
18/592
|
5.6%
33/591
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862 778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee Disclosure Restriction Description: 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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER