Back to resultsEfficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
Primary Purpose
Essential Hypertension
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Valsartan 160 mg capsules
Amlodipine 5 mg capsules
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Essential Hypertension focused on measuring Essential hypertension, blood pressure, edema, valsartan, amlodipine, combination treatment
Eligibility Criteria
Inclusion Criteria:
- Male or female outpatients ≥ 55 years of age
- Patients with essential hypertension measured using a validated automated oscillometric device at Visit 1
- Non-treated patients must have a MSSBP ≥ 140 mmHg and ≤ 160 mmHg
- Patients pre-treated on monotherapy prior to Visit 1 must have MSSBP ≤ 160 mmHg
- To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥ 130 mmHg and ≤ 160 mmHg
- No peripheral edema at Visit 2 (randomization)
- Written informed consent to participate in this study prior to any study procedures
Exclusion Criteria:
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
- Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures
- Patients taking more than 1 antihypertensive medication at Visit 1
- Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of pre-treated patients that require tapering down of anti-hypertensive treatments. For patients with previous antihypertensive medication that require a gradual downward titration, the tapering down should be done according to manufacturers instructions and last dose should be taken by week -2 prior to randomization
- msSBP > 180 mmHg or msDBP > 110 mmHg at any time between Visit 1 and Visit 2
- Evidence of a secondary form of hypertension, including but not limited to any of the following: Coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, polycystic kidney disease, or pheochromocytoma
- History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1
- History of heart failure Grade II - IV according to the NYHA classification
- Second or third degree heart block with or without a pacemaker
- Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
- Concomitant unstable angina pectoris
- Clinically significant valvular heart disease
- Patients with Type 1 diabetes mellitus
- Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator's judgment. It is recommended that Type 2 diabetic patients are adequately controlled and, if treated with medication, be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1
- Evidence of hepatic disease as determined by one of the following: AST or ALT values > 2x UNL at study entry, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
- Evidence of renal impairment as determined by one of the following: serum creatinine > 1.5 x UNL at visit 1, history of dialysis, or history of nephrotic syndrome
- Serum potassium values > 5.5 mmol/L at study entry
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
- Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, places the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study period
- Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
- Any severe, life-threatening disease within the past five years
- History of drug or alcohol abuse within the last 2 years
- Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
- Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent
- Persons directly involved in the execution of this protocol
Sites / Locations
- sites in Argentina
- sites in Chile
- sites in Ecuador
- sites in Finland
- sites in France
- sites in Germany
- sites in Italy
- sites in Norway
- sites in Spain
- sites in Sweden
- sites in Switzerland
- sites in Turkey
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Valsartan/amlodipine 160/5 mg
Amlodipine 10 mg
Arm 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.
Outcomes
Primary Outcome Measures
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
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.
Percentage of Patients With Peripheral Edema From Baseline to Week 8
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.
Secondary Outcome Measures
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
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.
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to 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. 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.
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
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.
Full Information
NCT ID
NCT00437645
First Posted
February 16, 2007
Last Updated
November 3, 2014
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00437645
Brief Title
Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
Official Title
A Double-blind, Randomized, Multicenter, Parallel Group Study to Evaluate the Efficacy, Tolerability, and Safety of Treatment With the Combination of Valsartan/Amlodipine 160/5 mg Compared to Amlodipine 10 mg in Patients With Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Alone
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
November 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
This study was designed to compare the efficacy, tolerability, and safety of the combination valsartan/amlodipine 160/5 mg versus amlodipine 10 mg in patients with essential hypertension not adequately controlled (defined as mean sitting systolic blood pressure [msSBP] ≥ 130 mmHg and ≤ 160 mmHg) on amlodipine 5 mg alone. The study evaluated both the efficacy and tolerability of the treatments by providing data that assessed blood pressure and the proportion of patients developing peripheral edema.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Hypertension
Keywords
Essential hypertension, blood pressure, edema, valsartan, amlodipine, combination treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1183 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Valsartan/amlodipine 160/5 mg
Arm Type
Experimental
Arm 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.
Arm Title
Amlodipine 10 mg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Valsartan 160 mg capsules
Intervention Type
Drug
Intervention Name(s)
Amlodipine 5 mg capsules
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
capsules
Primary Outcome Measure Information:
Title
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
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
Title
Percentage of Patients With Peripheral Edema From Baseline to Week 8
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
Secondary Outcome Measure Information:
Title
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
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
Title
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
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
Title
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female outpatients ≥ 55 years of age
Patients with essential hypertension measured using a validated automated oscillometric device at Visit 1
Non-treated patients must have a MSSBP ≥ 140 mmHg and ≤ 160 mmHg
Patients pre-treated on monotherapy prior to Visit 1 must have MSSBP ≤ 160 mmHg
To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥ 130 mmHg and ≤ 160 mmHg
No peripheral edema at Visit 2 (randomization)
Written informed consent to participate in this study prior to any study procedures
Exclusion Criteria:
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures
Patients taking more than 1 antihypertensive medication at Visit 1
Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of pre-treated patients that require tapering down of anti-hypertensive treatments. For patients with previous antihypertensive medication that require a gradual downward titration, the tapering down should be done according to manufacturers instructions and last dose should be taken by week -2 prior to randomization
msSBP > 180 mmHg or msDBP > 110 mmHg at any time between Visit 1 and Visit 2
Evidence of a secondary form of hypertension, including but not limited to any of the following: Coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, polycystic kidney disease, or pheochromocytoma
History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1
History of heart failure Grade II - IV according to the NYHA classification
Second or third degree heart block with or without a pacemaker
Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
Concomitant unstable angina pectoris
Clinically significant valvular heart disease
Patients with Type 1 diabetes mellitus
Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator's judgment. It is recommended that Type 2 diabetic patients are adequately controlled and, if treated with medication, be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1
Evidence of hepatic disease as determined by one of the following: AST or ALT values > 2x UNL at study entry, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
Evidence of renal impairment as determined by one of the following: serum creatinine > 1.5 x UNL at visit 1, history of dialysis, or history of nephrotic syndrome
Serum potassium values > 5.5 mmol/L at study entry
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, places the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study period
Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
Any severe, life-threatening disease within the past five years
History of drug or alcohol abuse within the last 2 years
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent
Persons directly involved in the execution of this protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
sites in Argentina
City
Agentina
Country
Argentina
Facility Name
sites in Chile
City
Chile
Country
Chile
Facility Name
sites in Ecuador
City
Ecuador
Country
Ecuador
Facility Name
sites in Finland
City
Finland
Country
Finland
Facility Name
sites in France
City
France
Country
France
Facility Name
sites in Germany
City
Germany
Country
Germany
Facility Name
sites in Italy
City
Italy
Country
Italy
Facility Name
sites in Norway
City
Norway
Country
Norway
Facility Name
sites in Spain
City
Spain
Country
Spain
Facility Name
sites in Sweden
City
Sweden
Country
Sweden
Facility Name
sites in Switzerland
City
Switzerland
Country
Switzerland
Facility Name
sites in Turkey
City
Turkey
Country
Turkey
12. IPD Sharing Statement
Citations:
PubMed Identifier
19196360
Citation
Schrader J, Salvetti A, Calvo C, Akpinar E, Keeling L, Weisskopf M, Brunel P. The combination of amlodipine/valsartan 5/160 mg produces less peripheral oedema than amlodipine 10 mg in hypertensive patients not adequately controlled with amlodipine 5 mg. Int J Clin Pract. 2009 Feb;63(2):217-25. doi: 10.1111/j.1742-1241.2008.01977.x.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
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