Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Valsartan 160 mg capsules; Amlodipine 5 mg capsules; placebo
Intervention description: capsules
Intervention MeSH terms: Amlodipine; Valsartan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1183.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Essential hypertension; blood pressure; edema; valsartan; amlodipine; combination treatment

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.
    

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