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

NCT00523549 | Completed Phase 4 Results

• 1 other identifier: CVAA489AUS01
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertension; Diastolic Dysfunction

Keywords

Hypertension; systolic blood pressure; diastolic dysfunction; valsartan; amlodipine

Outcome Measures

Primary Outcomes (1)

• Change in Lateral Mitral Annular Myocardial Relaxation Velocity

  Change from baseline in lateral mitral annular myocardial relaxation velocity (E') at Week 24

  Baseline to 24 weeks after treatment

Secondary Outcomes (6)

• Change in Left Atrial Size

  Baseline to 24 weeks after treatment

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

  Baseline to 24 weeks after treatment

• Percent Change From Baseline in Vascular Stiffness

  Baseline to 8 and 24 weeks after treatment

• Change in Mean Sitting Systolic Blood Pressure (msSBP)

  Baseline to 8 and 24 weeks after treatment

• Change in Mean Sitting Diastolic Blood Pressure (msDBP)

  Baseline to 8 and 24 weeks after treatment

Study Arms (2)

Standard treatment regimen

EXPERIMENTAL

(Valsartan + Amlodipine to target SBP of \< 140 mmHg)

Drug: valsartan; Drug: amlodipine

Intensive treatment regimen

EXPERIMENTAL

(Valsartan + Amlodipine to target SBP \< 130 mm Hg)

Drug: valsartan; Drug: amlodipine

Interventions

valsartan DRUG

160 mg or 320 mg tablets once a day

Also known as: Diovan

Intensive treatment regimen; Standard treatment regimen

amlodipine DRUG

5 mg or 10 mg tablets once a day

Also known as: Norvasc

Intensive treatment regimen; Standard treatment regimen

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Sites

USA, New Jersey, United States

Location

Related Publications (1)

• Solomon SD, Verma A, Desai A, Hassanein A, Izzo J, Oparil S, Lacourciere Y, Lee J, Seifu Y, Hilkert RJ, Rocha R, Pitt B; Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction Investigators. Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction. Hypertension. 2010 Feb;55(2):241-8. doi: 10.1161/HYPERTENSIONAHA.109.138529. Epub 2009 Dec 7.

  PMID: 19996069 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

Valsartan; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2007
• First Posted: August 31, 2007
• Study Start: November 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: April 23, 2012
• Results First Posted: March 10, 2011

Record last verified: 2012-04

Locations

US (1)