The Effects of Systolic Blood Pressure Lowering on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction
Condition: Hypertension; Diastolic Dysfunction
MeSH terms: Hypertension; Systolic Murmurs
Intervention: valsartan; amlodipine
Intervention description: 160 mg or 320 mg tablets once a day; 5 mg or 10 mg tablets once a day
Intervention MeSH terms: Amlodipine; Valsartan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 229.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Hypertension; systolic blood pressure; diastolic dysfunction; valsartan; amlodipine

Summary:

      The purpose of this study is to determine the effects of treatment with valsartan +
      amlodipine to a target systolic blood pressure (SBP)<130 mmHg compared to the Joint National
      Commission on the Treatment of Hypertension 7 recommended target SBP of <140 mmHg on the
      intrinsic diastolic properties of the myocardium in patients with hypertension and
      echocardiographic evidence of diastolic dysfunction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 45 years or older

          -  Male and female patients are eligible. Female patients must be post-menopausal for one
             year, surgically sterile, or using effective contraceptive methods such as a double
             barrier method with spermicide, an intra-uterine device, or hormonal contraceptives.
             Post-menopausal women on a stable dose of hormone replacement therapy (HRT) for at
             least three (3) months prior to the screening visit are eligible for the study.

          -  Uncontrolled systolic hypertension on a maximum of two (2) antihypertensive
             medications at the time of screening.

          -  Echocardiographic ejection fraction ≥50% and evidence of diastolic dysfunction.

          -  Provide written informed consent to participate in the study prior to any screening or
             study procedures

          -  Have the ability to communicate well and comply with all study requirements

        Exclusion Criteria:

          -  Severe hypertension defined as a MSSBP >200 mmHg and/or MSDBP >120 mmHg.

          -  History of a secondary cause of hypertension including but not limited to: coarctation
             of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis,
             Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.

          -  Ejection fraction <50 %

          -  History of stroke, transient ischemic attack, myocardial infarction, coronary artery
             bypass graft surgery, or unstable angina pectoris within 6 months of screening

          -  Presence of clinically significant ventricular or supraventricular arrhythmias (e.g.
             atrial fibrillation/flutter)

          -  History of congestive heart failure

          -  History of diabetes mellitus

          -  History of renal impairment with serum creatinine >2.0 mg/dL at screening, history of
             dialysis, or history of nephritic syndrome

          -  Antihypertensive therapy with three (3) or more medications at the time of screening

          -  Active and/or treated malignancy of any organ system within twelve (12) months of
             enrollment, with the exception of localized basal cell carcinoma of the skin

          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test (>5 mIU/ml)

          -  Women of child-bearing potential (WOCBP), defined as all women physiologically capable
             of becoming pregnant, including women whose career, lifestyle, or sexual orientation
             precludes intercourse with a male partner and women whose partners have been
             sterilized by vasectomy or other means, UNLESS they meet the following definition of
             post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of
             spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical
             bilateral oophorectomy with or without hysterectomy OR are using one or more of the
             following acceptable methods of contraception: barrier method with spermicidal agent,
             an intrauterine device, hormonal contraceptives, or total abstinence at the discretion
             of the investigator in cases where the age, career, lifestyle, or sexual orientation
             of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation,
             symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
             contraception. Reliable contraception should be maintained throughout the study

          -  Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of any drug including, but not limited to, any
             of the following: history of major gastrointestinal tract surgery such as gastrectomy,
             gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric
             banding, currently active, or active inflammatory bowel syndrome within 12 months
             prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal
             bleeding, or urinary tract obstruction regarded as clinically meaningful by the
             investigator

          -  Pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury
             within 12 months prior to Visit 1

          -  Any serum AST or ALT elevation two (2) times the upper limit of normal

        Other protocol-defined inclusion/exclusion criteria may apply