The Effects of Systolic Blood Pressure Lowering on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction

Condition(s) targeted: Hypertension; Diastolic Dysfunction

Intervention: valsartan (Drug); amlodipine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

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.

Official title: A Multi-center, Prospective, Randomized, Open-label Study With Blinded Outcome Evaluation to Evaluate the Effects of Systolic Blood Pressure Lowering to Different Targets (Less Than 130 mmHg vs. Less Than 140 mmHg) on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in Lateral Mitral Annular Myocardial Relaxation Velocity

Secondary outcome:

Change in Left Atrial Size

Change in Ratio of Peak E Wave Velocity/Lateral Mitral Annular Myocardial Relaxation Velocity

Percent Change From Baseline in Vascular Stiffness

Change in Mean Sitting Systolic Blood Pressure (msSBP)

Change in Mean Sitting Diastolic Blood Pressure (msDBP)

Change in Estimated Central Aortic Pressure

Minimum age: 45 Years. Maximum age: N/A. Gender(s): Both.

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

Novartis Investigative Sites, USA, New Jersey, United States

Starting date: November 2006
Last updated: April 19, 2012