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

NCT00149227 | Completed Phase 4 Results DMC

• 1 other identifier: KHS2004
• Study Type: interventional
• Target: 3,031
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Ischemic Heart Disease; Congestive Heart Failure; Stroke

Keywords

High risk hypertension; Ischemic heart disease; Angiotensin receptor blockers; Cardiovascular mortality- morbidity; KYOTO HEART Study

Outcome Measures

Primary Outcomes (9)

• 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.

  five years

• 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.

  five years

• 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.

  five years

• 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.

  five years

• 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.

  five years

• Operation of PCI or Bypass Operation

  five years

• 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.

  five years

• 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.

  five years

• 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.

  five years

Secondary Outcomes (5)

• All Cause Mortality

  five years

• Worsening of Cardiac Function

  five years

• New Onset or Worsening of Arrhythmias

  five years

• New Onset or Worsening of Diabetes Mellitus or IGT

  five years

• Uncontrolled Blood Pressure, Etc.

  five years

Study Arms (2)

Non-ARB

ACTIVE COMPARATOR

'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs

Drug: Non-ARB

Valsartan

EXPERIMENTAL

Valsartan add-on treatment

Drug: Valsartan

Interventions

Valsartan DRUG

Valsartan add-on arm: valsartan 40-160 mg per day, and an additional antihypertensive drugs other than ARB and ACEI are administered if necessary.

Also known as: Diovan

Valsartan

Non-ARB DRUG

'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs

Also known as: Conventional anti-hypertensive treatment

Non-ARB

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Kyoto Prefectural University of Medicine: lead

Study Sites (1)

Kyoto Prefectural University of Medicine

Kyoto, Kyoto, 602-8566, Japan

Location

Related Publications (2)

• 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.

  PMID: 18800142 BACKGROUND

• 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.

  PMID: 19723695 RESULT

MeSH Terms

Conditions

Hypertension; Myocardial Ischemia; Heart Failure; Stroke

Interventions

Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System 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

Limitations and Caveats

The study was performed using PROBE design, which does not exclude possible bias for softer endpoints such as angina and TIA. However, all softer endpoints were diagnosed by CAG and CT/MRI. We believe that under reporting would be unlikely.

Results Point of Contact

• Title: Prof. Hiroaki Matsubara
• Organization: Department of Cardiology, Kyoto Prefectural University of Medicine

matsubah@koto.kpu-m.ac.jp

+81-75-251-5511

Study Officials

• Hiroaki Matsubara, MD,PhD

  Kyoto Prefectural University of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: January 1, 2004
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: December 12, 2012
• Results First Posted: December 12, 2012

Record last verified: 2012-12

Locations

JP (1)