Back to resultsAdd-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
Primary Purpose
Hypertension, Ischemic Heart Disease, Congestive Heart Failure
Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Valsartan
Non-ARB
Sponsored by
About this trial
This is an interventional diagnostic trial for Hypertension focused on measuring High risk hypertension, Ischemic heart disease, Angiotensin receptor blockers, Cardiovascular mortality- morbidity, KYOTO HEART Study
Eligibility Criteria
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.)
Sites / Locations
- Kyoto Prefectural University of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Non-ARB
Valsartan
Arm Description
'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs
Valsartan add-on treatment
Outcomes
Primary Outcome Measures
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
Operation of PCI or Bypass Operation
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
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 significance with a two-tailed 5% statistical significant level.
Secondary Outcome Measures
All Cause Mortality
Worsening of Cardiac Function
New Onset or Worsening of Arrhythmias
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 significance with a two-tailed 5% statistical significant level.
Uncontrolled Blood Pressure, Etc.
Full Information
NCT ID
NCT00149227
First Posted
September 6, 2005
Last Updated
December 9, 2012
Sponsor
Kyoto Prefectural University of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT00149227
Brief Title
Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
Official Title
Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kyoto Prefectural University of Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Ischemic Heart Disease, Congestive Heart Failure, Stroke
Keywords
High risk hypertension, Ischemic heart disease, Angiotensin receptor blockers, Cardiovascular mortality- morbidity, KYOTO HEART Study
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3031 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Non-ARB
Arm Type
Active Comparator
Arm Description
'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs
Arm Title
Valsartan
Arm Type
Experimental
Arm Description
Valsartan add-on treatment
Intervention Type
Drug
Intervention Name(s)
Valsartan
Other Intervention Name(s)
Diovan
Intervention Description
Valsartan add-on arm: valsartan 40-160 mg per day, and an additional antihypertensive drugs other than ARB and ACEI are administered if necessary.
Intervention Type
Drug
Intervention Name(s)
Non-ARB
Other Intervention Name(s)
Conventional anti-hypertensive treatment
Intervention Description
'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs
Primary Outcome Measure Information:
Title
New Onset or Recurrence of Stroke
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
New Onset or Recurrence of Transient Ischemic Attack
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
New Onset or Recurrence of Acute Myocardial Infarction
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
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
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
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
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
Operation of PCI or Bypass Operation
Time Frame
five years
Title
New Onset of Acute Dissecting Aneurysm of the Aorta
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
New Onset, Recurrence or Worsening of Arteriosclerosis Obliterans
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
Transition to Dialysis, Doubling of Plasma Cr Levels
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Secondary Outcome Measure Information:
Title
All Cause Mortality
Time Frame
five years
Title
Worsening of Cardiac Function
Time Frame
five years
Title
New Onset or Worsening of Arrhythmias
Time Frame
five years
Title
New Onset or Worsening of Diabetes Mellitus or IGT
Description
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 significance with a two-tailed 5% statistical significant level.
Time Frame
five years
Title
Uncontrolled Blood Pressure, Etc.
Time Frame
five years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroaki Matsubara, MD,PhD
Organizational Affiliation
Kyoto Prefectural University of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Kyoto Prefectural University of Medicine
City
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
18800142
Citation
Sawada T, Takahashi T, Yamada H, Dahlof 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.
Results Reference
background
PubMed Identifier
19723695
Citation
Sawada T, Yamada H, Dahlof 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/eurheartj/ehp363. Epub 2009 Aug 31.
Results Reference
result
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Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
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