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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

Journal of Human Hypertension volume 23, pages 188–195 (2009)Cite this article

A Corrigendum to this article was published on 14 August 2013

Abstract

It remains to be determined whether the evidence in Western countries for blockade of the renin–angiotensin System in cardiovascular diseases could be directly applied to East Asian races including the Japanese population as a long-term strategy. The KYOTO HEART Study (KHS) is designed to investigate the add-on effect of valsartan versus conventional anti-hypertensive treatment on cardiovascular morbidity and mortality in Japanese hypertensive patients with uncontrolled blood pressure and with high cardiovascular risk. Over 3000 high-risk Japanese patients with uncontrolled hypertension were randomised to receive either additional treatment with valsartan or conventional non-angiotensin receptor blocker therapies, and the follow-up period will be at least 3 years. The primary end point is a composite of defined cardio- or cerebro-vascular events. Secondary end points include all causes of mortality, worsening of cardiac function, new onset or worsening of arrhythmias or diabetes mellitus. The KHS will provide new evidence for the management of blood pressure in hypertensive patients with high risk.

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Acknowledgements

Role of the funding source: The study was funded by Kyoto Prefectural University School of Medicine, with an unrestricted grant from Novartis Pharma KK, Japan. The sponsor had no role in study design, data collection, data analysis, data interpretation or writing of the report. The executive committee will have full access to all the data at the end of the study, and has final responsibility for the decision to submit for publication.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Kyoto Prefectural University School of Medicine, Kyoto, Japan

    T Sawada, T Takahashi, H Yamada & H Matsubara

  2. Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden

    B Dahlöf

Authors
  1. T Sawada
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  2. T Takahashi
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  3. H Yamada
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  4. B Dahlöf
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  5. H Matsubara
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Consortia

for the KYOTO HEART Study Group

Corresponding author

Correspondence to T Sawada.

Appendix

Appendix

Organisation and data management

Matsubara H supervises the KYOTO HEART Study (KHS) as the chief investigator, and several staff have been appointed by the chief investigator to support the management of the study as representatives of the KHS group secretariat. The KHS is administered by the Steering Committee, which is composed of academic leaders appointed by the chief investigator. The role of the Steering Committee is to supervise the overall execution of the study.

In the KHS, the Data and Safety Monitoring Board (DSMB), the Endpoint Committee and the Safety Committee are organised independently from the study group and each organisation consists of three external experts. The DSMB members are blinded to the allocation of drug treatment groups, meet periodically, have a stopping guideline for terminating the trial prematurely and make recommendations to the Steering Committee about the ethical aspects of trial continuation by evaluating each case of possible adverse events. This study will finish when the number of primary endpoints reaches the hypothesis after the end of enrolment. The DSMB will review the effectiveness and safety of the study at regular intervals. This board executes three interim analyses, with the O'Brien–Fleming method. Yagi K, who is a chief biostatistician at the Louis Pasteur Center for Medical Research, Kyoto, Japan, appointed the DSMB members consisting of two physicians who are independent of the study. The Endpoint Committee and the Safety Committee are blinded to the allocation of drug treatment groups and the results of the study, and are managed separately from investigators and biostatisticians. The Safety Committee has the role to oversee the welfare of patients enroled in the trial from the ethical point of view. In addition, the Substudy committee is organised according to the agreement of the Steering Committee. Investigators are blinded to the allocation of drug treatment groups and the results of the study until the discontinuation report from the DSMB or the final report of the study data analysis is announced.

Data collection and management, and allocation for drug treatment groups are conducted by the automatic electronic data-capturing system using the wide area network with a secure server managed by the data centre in Kobe, which is independent of the study implementation group. The statistical analysis of the data is performed by the biostatisticians at the Louis Pasteur Center for Medical Research, Kyoto, Japan, who are blinded to the allocation of drug treatment groups and independent of the study implementation group and the funding source. The Data monitoring team periodically visits randomly selected investigators to check the suitability between the hospital data and the input data presented by internet network system.

Executive committee

H Matsubara, Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine is the study chairman. B Dahlöf, Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden, is the honorary supervisor of the logistics, and conducts the reporting of the study.

Steering committee

Kyoto Prefectural University of Medicine—T Sawada (Main Steering Committee Member), T Shirayama, Y Mori, M Okigaki, A Matsumuro, H Yamada, Y Tsutsumi, M Matoba, T Takahashi, H Shiraishi, K Ikeda, T Nakamura and T Yamada; National Hospital Organization Maizuru Medical Center—S Hirano; National Hospital Organization Shiga Hospital—A Azuma; Kyoto Prefectural Yosanoumi Hospital—S Kimura; Akashi Municipal Hospital—S Sasaki; Ayabe City Hospital—K Shiga; Omihachiman Community Medical Center—K Maki; Kyoto City Hospital—K Furukawa; Kumihama Hospital—S Okuda; Nantan General Hospital—Y Kajita; Fukuchiyama City Hospital—M Nishio; Kyoto First Red Cross Hospital—Y Kohno; Kyoto Second Red Cross Hospital—M Kitamura; Maizuru Red Cross Hospital—K Nishida; Saiseikai Kyoto Hospital—Y Yamahara; Saiseikai Shiga Hospital—T Nakamura; Uji Hospital—S Sawada; Gakkentoshi Hospital—R Sakai; Kameoka Municipal Hospital—T Kuriyama; Kyoto Kizugawa Hospital—H Miyanaga; Kyoto Interdisciplinary Institute Hospital of Community Medicine—T Kitani; Social Insurance Kyoto Hospital—H Haruyama; Shakaihoken Kobe Central Hospital—A Nishio; Kouseikai Takeda Hospital—N Kinoshita; Aijyukai Dohjin Hospital—S Inagaki; Matsushita Memorial Hospital—H Sugihara; Aiseikai Yamashina Hospital—M Katamura; Midorigaoka Hospital—T Hachiya; Asahi University Murakami Memorial Hospital—S Kato; Meiji University of Oriental Medicine Hospital—K Ohtsuki.

Endpoint committee

J Higaki, Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Japan; S Kim-Mitsuyama, Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; T Ichiki, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Safety committee

M Kitakaze, Department of Cardiovascular Medicine, National Cardiovascular Center, Osaka, Japan; T Sugiura, Department of Clinical Laboratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan; H Rakugi, Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

Data and safety monitoring board

K Yagi, Louis Pasteur Center for Medical Research, Kyoto, Japan; K Kanda, Department of Cardiovascular surgery, Division of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; C Sakakura, Department of Digestive Surgery, Division of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Statistical analysis organization

K Yagi, Louis Pasteur Center for Medical Research, Kyoto, Japan; Nobuo Shirahashi, Department of Preventive Medicine and Environmental Health, Osaka City University Medical School, Osaka, Japan.

Data monitoring board

M Miki, Kyoto Prefectural University School of Medicine, Kyoto, Japan; S Toyoda, Kyoto Prefectural University School of Medicine, Kyoto, Japan.

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Sawada, T., Takahashi, T., Yamada, H. et al. 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 23, 188–195 (2009). https://doi.org/10.1038/jhh.2008.116

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