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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00437645
First received: February 16, 2007
Last updated: March 31, 2011
Last verified: March 2011

February 16, 2007
March 31, 2011
January 2007
November 2007   (final data collection date for primary outcome measure)
  • 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.
  • Incidence of peripheral edema quantified as adverse event (AE) reported peripheral edema after 8-week treatment
  • Change in mean sitting systolic blood pressure (MSSBP) after 8-week treatment
Complete list of historical versions of study NCT00437645 on ClinicalTrials.gov Archive Site
  • 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.
  • Change in mean sitting diastolic blood pressure (MSDBP) after 8-week treatment
  • Change from baseline in MSSBP and MSDBP after 4 and 12 weeks of treatment
  • Systolic blood pressure responder rate (defined as MSSBP < 130 mmHg or ≥ 20 mmHg reduction from baseline) at week 4, 8, and 12
  • Proportion of patients who reach systolic blood pressure control (defined as MSSBP < 130mmHg) at week 4, 8, and 12
  • Proportion of patients who reach overall blood pressure control (defined as BP <140/90 mmHg for non-diabetic patients and < 130/80 mmHg for diabetic patients) at week 4, 8, and 12
Not Provided
Not Provided
 
Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Essential Hypertension
  • Drug: Valsartan 160 mg capsules
  • Drug: Amlodipine 5 mg capsules
  • Drug: placebo
    capsules
  • 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.
    Interventions:
    • Drug: Valsartan 160 mg capsules
    • Drug: Amlodipine 5 mg capsules
    • Drug: placebo
  • 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.
    Interventions:
    • Drug: Valsartan 160 mg capsules
    • Drug: Amlodipine 5 mg capsules
    • Drug: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1183
November 2007
November 2007   (final data collection date for primary outcome measure)

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
Both
55 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Chile,   Ecuador,   Finland,   France,   Germany,   Italy,   Norway,   Spain,   Sweden,   Switzerland,   Turkey
 
NCT00437645
CVAA489A2404
Not Provided
Study Director, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP