ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00437645
Recruitment Status : Completed
First Posted : February 21, 2007
Results First Posted : February 14, 2011
Last Update Posted : November 11, 2014
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Essential Hypertension
Interventions Drug: Valsartan 160 mg capsules
Drug: Amlodipine 5 mg capsules
Drug: placebo
Enrollment 1183
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 592 591
Completed 557 476
Not Completed 35 115
Reason Not Completed
Adverse Event             15             84
Withdrawal by Subject             10             22
Protocol Violation             3             3
Lost to Follow-up             2             3
Administrative problems             2             1
Lack of Efficacy             2             1
Condition no longer requires study drug             1             1
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 592 591 1183
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Age (years)
Overall study Number Analyzed 592 participants 591 participants 1183 participants
65.6  (7.56) 65.4  (7.16) 65.5  (7.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 592 participants 591 participants 1183 participants
Female
285
  48.1%
284
  48.1%
569
  48.1%
Male
307
  51.9%
307
  51.9%
614
  51.9%
1.Primary Outcome
Title Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
Hide Description 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.
Time Frame Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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]).
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 567 510
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-8.01  (0.5944) -6.30  (0.6088)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valsartan/Amlodipine 160/5 mg, Amlodipine 10 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Statistical analysis for non-inferiority of valsartan/amlodipine 160/5 mg to amlodipine 10 mg alone with a non-inferiority margin of 3 mm Hg
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-3.00 to -0.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.65
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Patients With Peripheral Edema From Baseline to Week 8
Hide Description 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.
Time Frame Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: All randomized patients.
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 592 591
Measure Type: Number
Unit of Measure: Percentage of patients
6.6 31.1
3.Secondary Outcome
Title Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
Hide Description 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.
Time Frame Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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]).
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 567 510
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-4.65  (0.3616) -4.13  (0.3690)
4.Secondary Outcome
Title Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
Hide Description 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.
Time Frame Baseline to Weeks 4, 8, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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]).
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 576 535
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
msSBP: Week 4 (n=576, 535) -8.40  (0.5559) -6.48  (0.5676)
msSBP: Week 8 (n=567, 510) -8.15  (0.6065) -6.11  (0.6266)
msSBP: Week 12 (n=569, 531) -9.08  (0.6968) -7.82  (0.7088)
msDBP: Week 4 (n=576, 535) -5.05  (0.3559) -4.23  (0.3623)
msDBP: Week 8 (n=576, 510) -4.68  (0.3632) -3.97  (0.3736)
msDBP: Week 12 (n=569, 531) -5.50  (0.03735) -4.90  (0.3785)
5.Secondary Outcome
Title Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
Hide Description 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.
Time Frame Baseline to Weeks 4, 8, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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]).
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 576 535
Measure Type: Number
Unit of Measure: Percentage of patients
Week 4 (n=576, 535) 35.07 25.42
Week 8 (n=567, 510) 34.22 25.49
Week 12 (n=569, 531) 37.96 31.26
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   11/592 (1.86%)   8/591 (1.35%) 
Cardiac disorders     
Atrial fibrillation  1  1/592 (0.17%)  0/591 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  0/592 (0.00%)  1/591 (0.17%) 
Gastrointestinal necrosis  1  0/592 (0.00%)  1/591 (0.17%) 
Inguinal hernia  1  0/592 (0.00%)  1/591 (0.17%) 
General disorders     
Asthenia  1  1/592 (0.17%)  0/591 (0.00%) 
Pyrexia  1  1/592 (0.17%)  0/591 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  2/592 (0.34%)  0/591 (0.00%) 
Cholelithiasis  1  1/592 (0.17%)  0/591 (0.00%) 
Infections and infestations     
Hantavirus pulmonary infection  1  1/592 (0.17%)  0/591 (0.00%) 
Urinary tract infection  1  1/592 (0.17%)  0/591 (0.00%) 
Injury, poisoning and procedural complications     
Drug toxicity  1  1/592 (0.17%)  0/591 (0.00%) 
Humerus fracture  1  0/592 (0.00%)  1/591 (0.17%) 
Ligament rupture  1  1/592 (0.17%)  0/591 (0.00%) 
Meniscus lesion  1  1/592 (0.17%)  0/591 (0.00%) 
Investigations     
Blood creatine phosphokinase increased  1  1/592 (0.17%)  0/591 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/592 (0.17%)  0/591 (0.00%) 
Bursitis  1  1/592 (0.17%)  0/591 (0.00%) 
Muscular weakness  1  0/592 (0.00%)  1/591 (0.17%) 
Myalgia  1  1/592 (0.17%)  0/591 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer  1  1/592 (0.17%)  0/591 (0.00%) 
Pancreatic carcinoma  1  0/592 (0.00%)  1/591 (0.17%) 
Nervous system disorders     
Cerebrovascular accident  1  0/592 (0.00%)  1/591 (0.17%) 
Dysphasia  1  0/592 (0.00%)  1/591 (0.17%) 
Psychiatric disorders     
Neglect of personal appearance  1  0/592 (0.00%)  1/591 (0.17%) 
Renal and urinary disorders     
Bladder tamponade  1  1/592 (0.17%)  0/591 (0.00%) 
Haematuria  1  1/592 (0.17%)  0/591 (0.00%) 
Renal impairment  1  1/592 (0.17%)  0/591 (0.00%) 
Reproductive system and breast disorders     
Epididymitis  1  0/592 (0.00%)  1/591 (0.17%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/592 (0.00%)  1/591 (0.17%) 
Haemoptysis  1  0/592 (0.00%)  1/591 (0.17%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  0/592 (0.00%)  1/591 (0.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Valsartan/Amlodipine 160/5 mg Amlodipine 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   61/592 (10.30%)   201/591 (34.01%) 
General disorders     
Oedema peripheral  1  43/592 (7.26%)  186/591 (31.47%) 
Nervous system disorders     
Headache  1  18/592 (3.04%)  33/591 (5.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Responsible Party: Study Director, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00437645     History of Changes
Other Study ID Numbers: CVAA489A2404
First Submitted: February 16, 2007
First Posted: February 21, 2007
Results First Submitted: August 17, 2009
Results First Posted: February 14, 2011
Last Update Posted: November 11, 2014