Essential HypertensionPhase 3NCT00437645
Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
A Phase 3 study testing Valsartan 160 mg capsules and Amlodipine 5 mg capsules in people with Essential Hypertension, run by Novartis Pharmaceuticals at 12 sites in 12 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Valsartan 160 mg capsules and Amlodipine 5 mg capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,183 participants
- Where
- 12 sitesin 12 countries
- Study dates
- Jan 2007to Nov 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
12 sites in 12 countries.
12 sites in 12 countries
About this study
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
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.
- Conditions
- Essential Hypertension
- Being tested
- Valsartan 160 mg capsules, Amlodipine 5 mg capsules, placebo
- Keywords
- Essential hypertension, blood pressure, edema, valsartan, amlodipine, combination treatment
- Medical subject headings
- Essential Hypertension, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valsartan 160 mg capsulesDrug
Amlodipine 5 mg capsulesDrug
placeboDrug
capsules
| Study group | Role | What they receive |
|---|---|---|
| Valsartan/amlodipine 160/5 mg | Experimental | 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. Receives: Drug: Valsartan 160 mg capsules; Drug: Amlodipine 5 mg capsules; Drug: placebo |
| Amlodipine 10 mg | Active comparator | 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. Receives: Drug: Valsartan 160 mg capsules; Drug: Amlodipine 5 mg capsules; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 8
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.
Measured: Baseline to Week 8
Secondary outcomes (3)
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.
Measured: Baseline to Week 8
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.
Measured: Baseline to Weeks 4, 8, and 12
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.
Measured: Baseline to Weeks 4, 8, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2007 (estimated)
- Study startJan 2007
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis Pharmaceuticals, Study chair, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00437645
- Sponsor's protocol ID
- CVAA489A2404
- Status last verified
- Nov 2014
- First submitted
- 16 Feb 2007
- Last updated
- 11 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 19196360
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00437645
- Acronym / sponsor ID
- CVAA489A2404
- Conditions
- Essential Hypertension
- Keywords
- Essential hypertension, blood pressure, edema, valsartan, amlodipine, combination treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,183 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 21 Feb 2007 (estimated)
- Results
- Posted 14 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valsartan/amlodipine 160/5 mg | Experimental | Drug: Valsartan 160 mg capsules, Drug: Amlodipine 5 mg capsules, Drug: placeboTwelve (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 | Active comparator | Drug: Valsartan 160 mg capsules, Drug: Amlodipine 5 mg capsules, Drug: placeboEight (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. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valsartan 160 mg capsules | Drug | Amlodipine 10 mg, Valsartan/amlodipine 160/5 mg |
| Amlodipine 5 mg capsules | Drug | Amlodipine 10 mg, Valsartan/amlodipine 160/5 mg |
| placebocapsules | Drug | Amlodipine 10 mg, Valsartan/amlodipine 160/5 mg |
Primary outcome
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
Time frame: 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
Time frame: 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.
3 secondary outcomes
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
Time frame: Baseline to Week 8
Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
Time frame: Baseline to Weeks 4, 8, and 12
Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
Time frame: Baseline to Weeks 4, 8, and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19196360Schrader 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study chair
Novartis Pharmaceuticals
12 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valsartan 160 mg capsules and Amlodipine 5 mg capsules in people with Essential Hypertension, run by Novartis Pharmaceuticals at 12 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Argentina, Chile, Ecuador, Finland, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 (time frame: Baseline to Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00437645, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2014.