Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
This study has been completed.
Sponsor:
Novartis Pharmaceuticals
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00437645
First received: February 16, 2007
Last updated: March 31, 2011
Last verified: March 2011
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Essential Hypertension |
Drug: Valsartan 160 mg capsules Drug: Amlodipine 5 mg capsules Drug: placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline to Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline to Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]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.
| Enrollment: | 1183 |
| Study Start Date: | January 2007 |
| Study Completion Date: | November 2007 |
| Primary Completion Date: | November 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: Valsartan 160 mg capsules
Drug: Amlodipine 5 mg capsules
Drug: placebo
capsules
|
|
Active Comparator: 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.
|
Drug: Valsartan 160 mg capsules
Drug: Amlodipine 5 mg capsules
Drug: placebo
capsules
|
Eligibility| Ages Eligible for Study: | 55 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00437645
Locations
| Argentina | |
| sites in Argentina | |
| Agentina, Argentina | |
| Chile | |
| sites in Chile | |
| Chile, Chile | |
| Ecuador | |
| sites in Ecuador | |
| Ecuador, Ecuador | |
| Finland | |
| sites in Finland | |
| Finland, Finland | |
| France | |
| sites in France | |
| France, France | |
| Germany | |
| sites in Germany | |
| Germany, Germany | |
| Italy | |
| sites in Italy | |
| Italy, Italy | |
| Norway | |
| sites in Norway | |
| Norway, Norway | |
| Spain | |
| sites in Spain | |
| Spain, Spain | |
| Sweden | |
| sites in Sweden | |
| Sweden, Sweden | |
| Switzerland | |
| sites in Switzerland | |
| Switzerland, Switzerland | |
| Turkey | |
| sites in Turkey | |
| Turkey, Turkey | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Chair: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Study Director, Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT00437645 History of Changes |
| Other Study ID Numbers: | CVAA489A2404 |
| Study First Received: | February 16, 2007 |
| Results First Received: | August 17, 2009 |
| Last Updated: | March 31, 2011 |
| Health Authority: | United States: Food and Drug Administration Finland: Finnish Medicines Agency Argentina: Ministry of Health Chile: Instituto de Salud Publica de Chile Ecuador: Public Health Ministry Germany: BfArM Norway: Norwegian Medicines Agency Spain: Spanish Agency of Medicines Spain: Ministry of Health and Consumption Sweden: Medical Products Agency Switzerland: Swissmedic Turkey: Ministry of Health |
Keywords provided by Novartis:
|
Essential hypertension blood pressure edema |
valsartan amlodipine combination treatment |
Additional relevant MeSH terms:
|
Hypertension Vascular Diseases Cardiovascular Diseases Amlodipine Valsartan Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Cardiovascular Agents Therapeutic Uses Vasodilator Agents Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists |
ClinicalTrials.gov processed this record on May 23, 2013