Valsartan in Elderly Isolated Systolic Hypertension Study (VALISH)

Valsartan in Elderly Isolated Systolic Hypertension

The aim of this study is to compare the incidence of cardiovascular events between two target systolic blood pressure levels, below 140 mmHg and below 150 mmHg under treatment with valsartan in elderly isolated systolic hypertensive patients in Japan.

Study Overview

• Status: Completed
• Conditions: Aged; Systolic Hypertension
• Intervention / Treatment: Other: target blood pressure

Detailed Description

Although antihypertensive therapy has been proven to reduce cardiovascular morbidity and mortality, it is unclear how much blood pressure should be decreased in elderly patients with hypertension. The Valsartan in Elderly Isolated Systolic Hypertension (VALISH) study is a multicenter parallel-group study comparing the incidence of cardiovascular events between two target systolic blood pressure levels, below 140 mmHg and below 150 mmHg, under treatment with valsartan, an angiotensin II receptor blocker, as an initial antihypertensive drug in elderly patients with isolated systolic hypertension. The number of patients to be recruited is 3,000 and the duration of follow-up is at least 2 years. This 3,000-patient trial was designed with a two-sided α level of 0.05 and 80% power to detect the difference in incidence of cardiovascular events between the target blood pressure levels based on estimation of the cardiovascular events ratio as 21.5/1,000 patient-years and 29.1/1,000 patient-years for the two blood pressure levels. The VALISH study, a large-scale investigator-initiated trial in Japan, will determine whether age should be considered in setting target blood pressure in treatment of isolated systolic hypertension in elderly patients.

• Study Type: Interventional
• Enrollment (Actual): 3079
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • ING Corporation, 8-21, Shinjuku-ku, Tokyo, Japan, 162-0067
      • VALISH Data Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients aged over 70 years and less than 85 years, regardless of sex.
• Patients with stable seated systolic blood pressure of over 160 mmHg and diastolic blood pressure of less than 90 mmHg at two visits within 2 to 4 weeks.
• Previously untreated patients or patients who are on other therapy that can be converted to valsartan.

Exclusion Criteria:

• Patients with secondary hypertension or malignant hypertension.
• Patients with seated systolic blood pressure of over 200 mmHg.
• Patients with seated diastolic blood pressure of over 90 mmHg.
• Patients with a history of cerebrovascular disorder or myocardial infarction within 6 months prior to enrolment in the study.
• Patients who underwent coronary arterioplasty within 6 months prior to enrolment in the study or patients who will undergo coronary arterioplasty within 6 months after entry.
• Patients with severe heart failure (NYHA functional classification III and IV).
• Patients with severe aortic stenosis or valvular disease.
• Patients with atrial fibrillation, atrial flutter, or serious arrhythmia.
• Patients with renal dysfunction with serum creatinine level of over 2 mg/dL.
• Patients with serious liver dysfunction.
• Patients with a history of hypersensitivity to valsartan.
• Other patients who are judged to be inappropriate for the study by the investigator or sub-investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: strict control; systolic blood pressure control: less than 140 mm Hg	Other: target blood pressure
Active Comparator: moderate control; systolic blood pressure control: 140 mm Hg to 149 mm Hg	Other: target blood pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite cardiovascular events	sudden death, fatal or nonfatal stroke, fatal or nonfatal myocardial infarction, death because of heart failure, other cardiovascular death, unplanned hospitalization for cardiovascular disease, and renal dysfunction (doubling of serum creatinine to a level 2.0 mg per 100 mL or introduction of dialysis).	participants will be followed for the duration of the study, an expected median follow-up 3.07 years

Secondary Outcome Measures

Outcome Measure	Time Frame
sudden death	participants will be followed for the duration of the study, an expected median follow-up 3.07 years
stroke	participants will be followed for the duration of the study, an expected median follow-up 3.07 years
myocardial infarction	participants will be followed for the duration of the study, an expected median follow-up 3.07 years
heart failure	participants will be followed for the duration of the study, an expected median follow-up 3.07 years
hospitalization	participants will be followed for the duration of the study, an expected median follow-up 3.07 years
renal disorder	participants will be followed for the duration of the study, an expected median follow-up 3.07 years

Collaborators and Investigators

• Sponsor: VALISH study
• Collaborators: Japan Cardiovascular Research Foundation
• Investigators: Principal Investigator: Toshio Ogihara, MD, PhD, Department of Geriatric Medicine, Osaka University Graduate School of Medicine; Principal Investigator: Takao Saruta, MD, PhD, Department of Internal Medicine, Keio University School of Medicine

Publications and helpful links

General Publications

• Ogihara T, Saruta T, Matsuoka H, Shimamoto K, Fujita T, Shimada K, Imai Y, Nishigaki M. valsartan in elderly isolated systolic hypertension (VALISH) study: rationale and design. Hypertens Res. 2004 Sep;27(9):657-61. doi: 10.1291/hypres.27.657.
• Ogihara T, Saruta T, Rakugi H, Matsuoka H, Shimamoto K, Shimada K, Imai Y, Kikuchi K, Ito S, Eto T, Kimura G, Imaizumi T, Takishita S, Ueshima H; Valsartan in Elderly Isolated Systolic Hypertension Study Group. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 2010 Aug;56(2):196-202. doi: 10.1161/HYPERTENSIONAHA.109.146035. Epub 2010 Jun 7.
• Yano Y, Rakugi H, Bakris GL, Lloyd-Jones DM, Oparil S, Saruta T, Shimada K, Matsuoka H, Imai Y, Ogihara T. On-Treatment Blood Pressure and Cardiovascular Outcomes in Older Adults With Isolated Systolic Hypertension. Hypertension. 2017 Feb;69(2):220-227. doi: 10.1161/HYPERTENSIONAHA.116.08600. Epub 2017 Jan 3.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 8, 2005

Study Record Updates

• Last Update Posted (Estimate): June 4, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: valsartan; isolated systolic hypertension; target blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Heart Murmurs; Hypertension; Systolic Murmurs
• Other Study ID Numbers: VAL-200310