Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)

Stroke Clinical Trial

Official title:

Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00149227
• Other study ID #: KHS2004
• Status: Completed
• Phase: Phase 4
• First received: September 6, 2005
• Last updated: December 9, 2012
• Start date: January 2004
• Est. completion date: January 2009

Study information

• Verified date: December 2012
• Source: Kyoto Prefectural University of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The KYOTO HEART Study is to assess the add-on effect of valsartan, an Angiotensin-Receptor Blocker, on top of the conventional treatment in high risk patients in Japan with hypertension in terms of the morbidity and mortality.

Description:

Although many reports show that ACE inhibitors and angiotensin II receptor blockers (ARB) are superior for prevention of cardiovascular events, previous data are not enough for the patients who have more than one risk factor and for anti-atherosclerotic effects of ARB. In Japan, there were only a few large-scale trials for cardiovascular disease prevention, and it has not been clarified whether the evidence in Western countries could be unqualifiedly applied to Japanese patients as a long-range strategy. The KYOTO HEART Study is to assess the add-on effect of valsartan, an Angiotensin-Receptor Blocker, on top of the conventional treatment in high risk patients with hypertension in terms of the morbidity and mortality.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3031
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 79 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of hypertension

• Clinical diagnosis of one or more risk factors, such as diabetes, smoking habit, lipid metabolism abnormality, history of ischemic heart disease (IHD) or cerebrovascular disease, obesity (BMI>25), chronic heart failure (NYHA II-III), and electrocardiogram (ECG) abnormality (LVH)

Exclusion Criteria:

• Patients who have already been administered ARB

• Patients with IHD within 6 months after percutaneous coronary intervention(PCI), and who are stable but are going to implement PCI or coronary artery bypass grafting(CABG)

• Severe/malignant/secondary hypertensive patients

• Pregnant women and women of childbearing potential

• History of heart failure, unstable angina, myocardial infarction, PTCA, or CABG within the preceding 6 months

• Arrhythmia needed to be treated or accompanied with symptoms, second or third degree AV block

• Severe renal impairment (Serum creatinine >3.0 mg/dl)

• Severe hepatic impairment (Hepatic failure, Cirrhosis, etc.)

Study Design

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

Related Conditions & MeSH terms

• Congestive Heart Failure
• Coronary Artery Disease
• Heart Diseases
• Heart Failure
• Hypertension
• Ischemic Heart Disease
• Myocardial Ischemia
• Stroke

Intervention

Drug:
• Valsartan
Valsartan add-on arm: valsartan 40-160 mg per day, and an additional antihypertensive drugs other than ARB and ACEI are administered if necessary.
• Non-ARB
'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs

Locations

Country	Name	City	State
Japan	Kyoto Prefectural University of Medicine	Kyoto

Sponsors (1)

Lead Sponsor	Collaborator
Kyoto Prefectural University of Medicine

Country where clinical trial is conducted

Japan, 

References & Publications (2)

Sawada T, Takahashi T, Yamada H, Dahlöf B, Matsubara H; KYOTO HEART Study Group. Rationale and design of the KYOTO HEART study: effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high risk of cardiovascular events. J Hum Hypertens. 2009 Mar;23(3):188-95. doi: 10.1038/jhh.2008.116. Epub 2008 Sep 18. Erratum in: J Hum Hypertens. 2013 Sep;27(9):580. — View Citation

Sawada T, Yamada H, Dahlöf B, Matsubara H; KYOTO HEART Study Group. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J. 2009 Oct;30(20):2461-9. doi: 10.1093/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New Onset or Recurrence of Stroke	Stroke events included brain hemorrhage, infarction, and TIA. They required hospitalization with neurological symptoms and were diagnosed by CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	New Onset or Recurrence of Transient Ischemic Attack	Transient ischemic attack (TIA) was defined as hospitalization with sudden onset of neurological deficit persisting for less than 24 hrs, and without abnormal findings using by CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	New Onset or Recurrence of Acute Myocardial Infarction	Acute myocardial infarction was diagnosed with hospitalization, ECG- change, and biomarkers for myocardial infarction. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	Hospitalization Due to the New Onset, Recurrence or Worsening of Heart Failure and Additional Concomitant Use of Other Anti-heart Failure Agents or Increase of Dosage	Heart failure event was defined as requiring hospitalization and clinical symptoms together with left ventricular dysfunction by echocardiography according to the guidelines of the AHA/ACC. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	Hospitalization Due to the New Onset, Occurrence or Worsening of Angina Pectoris and Additional Concomitant Use of Other Anti-anginal Agents or Increase of Dosage	Angina pectoris event required hospitalization and was diagnosed by both ECG changes corresponding with chest symptoms and coronary angiography showing 75% stenosis according to AHA/ACC guidelines. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	Operation of PCI or Bypass Operation		five years	No
Primary	New Onset of Acute Dissecting Aneurysm of the Aorta	Dissecting aneurysm of the aorta required hospitalization and was diagnosed by imaging technique, CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	New Onset, Recurrence or Worsening of Arteriosclerosis Obliterans	Arteriosclerosis obliterans (ASO) event was diagnosed with symptoms and CT / MRI imaging. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Primary	Transition to Dialysis, Doubling of Plasma Cr Levels	The first of any events, "transition to dialysis" or "doubling of plasma Cr levels compared to the entry", occurring in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Secondary	All Cause Mortality		five years	No
Secondary	Worsening of Cardiac Function		five years	No
Secondary	New Onset or Worsening of Arrhythmias		five years	No
Secondary	New Onset or Worsening of Diabetes Mellitus or IGT	Diabetes mellitus was defined as fasting plasma glucose >=126 mg/dl, causal blood glucose >= 200 mg /dl, HbA1C >= 6.5%, and/or plasma glucose 2hr after 75g glucose load >= 200 mg/dl. The first of these events, "new onset diabetes" or "worsening diabetes following IGT", occurring in a specific patient was classified as an event to be counted in the secondary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical signi?cance with a two-tailed 5% statistical signi?cant level.	five years	No
Secondary	Uncontrolled Blood Pressure, Etc.		five years	No