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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hiroaki Matsubara, MD., PhD, Kyoto Prefectural University of Medicine
ClinicalTrials.gov Identifier:
NCT00149227
First received: September 6, 2005
Last updated: December 9, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Hypertension
Ischemic Heart Disease
Congestive Heart Failure
Stroke
Drug: Valsartan
Drug: Non-ARB
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension

Resource links provided by NLM:


Further study details as provided by Kyoto Prefectural University of Medicine:

Primary Outcome Measures:
  • New Onset or Recurrence of Stroke [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
  • New Onset of Acute Dissecting Aneurysm of the Aorta [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
    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 [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Worsening of Cardiac Function [ Time Frame: five years ] [ Designated as safety issue: No ]
  • New Onset or Worsening of Arrhythmias [ Time Frame: five years ] [ Designated as safety issue: No ]
  • New Onset or Worsening of Diabetes Mellitus or IGT [ Time Frame: five years ] [ Designated as safety issue: No ]
    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. [ Time Frame: five years ] [ Designated as safety issue: No ]

Enrollment: 3031
Study Start Date: January 2004
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Non-ARB
'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs
Drug: Non-ARB
'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs
Other Name: Conventional anti-hypertensive treatment
Experimental: Valsartan
Valsartan add-on treatment
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.
Other Names:
  • Valsartan
  • Diovan

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.

  Eligibility

Ages Eligible for Study:   20 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00149227

Locations
Japan
Kyoto Prefectural University of Medicine
Kyoto, Japan, 602-8566
Sponsors and Collaborators
Kyoto Prefectural University of Medicine
Investigators
Study Chair: Hiroaki Matsubara, MD,PhD Kyoto Prefectural University of Medicine
  More Information

Publications:
Responsible Party: Hiroaki Matsubara, MD., PhD, Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension, Kyoto Prefectural University of Medicine
ClinicalTrials.gov Identifier: NCT00149227     History of Changes
Other Study ID Numbers: KHS2004
Study First Received: September 6, 2005
Results First Received: July 5, 2011
Last Updated: December 9, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto Prefectural University of Medicine:
High risk hypertension
Ischemic heart disease
Angiotensin receptor blockers
Cardiovascular mortality- morbidity
KYOTO HEART Study

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Heart Failure
Hypertension
Ischemia
Stroke
Coronary Disease
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Valsartan
Antihypertensive Agents
Angiotensin Receptor Antagonists
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014