Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy

NCT ID: NCT01984749

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30

Brief Summary

The purpose of this study is to demonstrate the effect of febuxostat in preventing cerebral and cardiorenovascular events in elderly patients with hyperuricemia who are at risk for cerebral and cardiorenovascular disease.

Conditions

Hyperuricemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Febuxostat treatment group

Once daily after breakfast (generally within 30 minutes after eating)

Group Type: EXPERIMENTAL

Febuxostat

Intervention Type: DRUG

Febuxostat will be taken once daily after breakfast (generally within 30 minutes after eating) but can be taken around the time of breakfast even if no food has been eaten. When the dose is to be increased, the principal or sub-investigator will carry out any required examinations and tests as needed.

1. The starting dose of the investigational product (febuxostat) will be 10 mg/day.

2. The dose will be increased to 20 mg/day at Week 4.

3. The aim is to increase the dose to 40 mg/day at Week 8.

Non-febuxostat treatment group

No febuxostat treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Febuxostat

Febuxostat will be taken once daily after breakfast (generally within 30 minutes after eating) but can be taken around the time of breakfast even if no food has been eaten. When the dose is to be increased, the principal or sub-investigator will carry out any required examinations and tests as needed.

1. The starting dose of the investigational product (febuxostat) will be 10 mg/day.

2. The dose will be increased to 20 mg/day at Week 4.

3. The aim is to increase the dose to 40 mg/day at Week 8.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• (1) Patients 65 years of age or older at enrollment who are able to visit
• (2) Patients with hyperuricemia, who have a serum uric acid level >7.0 mg/dL and <= 9.0 mg/dL (7.0 mg/dL < serum uric acid level <= 9.0 mg/dL) within 2 months prior to enrollment
• (3) Patients at risk for any of the cerebral or cardiorenovascular diseases in i) through iv) below (i) Previous or current history of hypertension (ii) Previous or current history of type 2 diabetes mellitus (iii) Renal disorders (30 mL/min/1.73 m2 <= eGFR < 60 mL/min/1.73 m2 within 3 months prior to enrollment) (iv) Previous history of cerebral or cardiorenovascular disease for more than 3 months prior to enrollment (stroke [cerebral hemorrhage, cerebral infarction, or subarachnoid hemorrhage], coronary artery disease, vascular disease, or cardiac failure)
• (4) Patients who personally give written informed consent to participate in this study

Exclusion Criteria

• (1) Patients with gouty tophus, or patients with subjective symptoms of gouty arthritis within 1 year prior to enrollment
• (2) Patients with a previous history of hypersensitivity to febuxostat or allopurinol
• (3) Patients with malignant tumors
• (4) Patients with serious kidney disease, Acute kidney disease, nephrotic syndrome, dialysis patients, kidney transplant patients, eGFR < 30 mL/min/1.73 m2 , etc.
• (5) Patients with a previous history of acute coronary syndrome or stroke within 3 months prior to enrollment (cerebral hemorrhage, cerebral infarction, or subarachnoid hemorrhage)
• (6) Patients with a >= 50% increase in serum creatinine within 3 months prior to enrollment
• (7) Patients with severe hypertension characterized by systolic blood pressure >= 180 mmHg or diastolic blood pressure >= 110 mmHg within 3 months prior to enrollment
• (8) Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 or more times the upper limit of normal within 3 months prior to enrollment
• (9) Patients on any of the following medications at enrollment Mercaptopurine hydrate, azathioprine, vidarabine, or didanosine
• (10) Patients who receive any of the following medications for the treatment of hyperuricemia within 1 month prior to enrollment Allopurinol, benzbromarone, probenecid, bucolome, topiroxostat, or febuxostat
• (11) Patients who start, modify the dose of, or discontinue any of the following medications within 1 month prior to enrollment Losartan, irbesartan, fenofibrate, thiazide diuretics, or loop diuretics
• (12) Patients on hormone replacement therapy with estrogen (estrogenic hormone products)
• (13) Patients who have participated in other clinical research (including trials) within 6 months prior to enrollment (non-interventional observational research not excluded)
• (14) Patients otherwise judged by the principal or sub-investigator to be unsuitable for the study

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teijin Pharma Limited

INDUSTRY

Sponsor Role: collaborator

Freed Study Group

OTHER

Sponsor Role: lead

Responsible Party

Hisao Ogawa

Deputy Director General of the hospital, National Cerebral and Cardiovascular Center Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hisao Ogawa

Role: STUDY_CHAIR

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University

Locations

Hiramitsu Heart Clinic

Nagoya, Aichi-ken, Japan

Ogawa-naika Clinic

Nagoya, Aichi-ken, Japan

Shakaiiryohoｊin Koｊunkai Daido Hospital

Nagoya, Aichi-ken, Japan

Honjo Daiichi Hospital

Yurihonjō, Akita, Japan

Iriyouhoujin Siyadan Yanagisawakai Yanagisawaiin

Matsudo, Chiba, Japan

Matsuno Medical Clinic

Iyo-gun, Ehime, Japan

Ishite Matsumoto Naika Junkanki Clinic

Matsuyama, Ehime, Japan

Ehime Medical CO-OP Izumigawa Clinic

Niihama, Ehime, Japan

Hanaoka IC Clinic

Buzen, Fukuoka, Japan

Otonari Clinic

Chikushino-shi, Fukuoka, Japan

Saku Hospital

Fukuoka, Fukuoka, Japan

Tohaya Iin

Fukuoka, Fukuoka, Japan

Medical Cooperation Toseikai Goto Clinic

Kitakyushu, Fukuoka, Japan

ONGA NAKAMA Medical Association ONGA Hospital

Onga-gun, Fukuoka, Japan

Southern Tohoku Research Institute For Neuroscience Southern Tohoku Medical Clinic

Kōriyama, Fukushima, Japan

Iryohojin Shadan Seijinkai Kawade Iin

Gifu, Gifu, Japan

Kawai Naika Clinic

Gifu, Gifu, Japan

Miwa Clinic: Gastroenterology Hepatology

Gifu, Gifu, Japan

Sagou Clinic

Gifu, Gifu, Japan

Sasaki Clinic

Gifu, Gifu, Japan

Takai Clinic

Gifu, Gifu, Japan

Takeda Clinic

Gifu, Gifu, Japan

Totani Medical Clinic

Gifu, Gifu, Japan

Noda Clinic

Ibi, Gifu, Japan

Sunomata Clinic

Ōgaki, Gifu, Japan

Tsurugaya Hospital

Isesaki, Gunma, Japan

Nakano Clinic

Shibukawa, Gunma, Japan

Iryouhoujinn Makikai Makibyouinn

Takasaki, Gunma, Japan

Shigenobu Clinic

Miyoshi, Hiroshima, Japan

Keiyukai Yoshida Hospital

Asahikawa, Hokkaido, Japan

Matsui Naika Clinic

Asahikawa, Hokkaido, Japan

Omiya Clinic

Asahikawa, Hokkaido, Japan

Miyanomori Memorial Hospital

Sapporo, Hokkaido, Japan

Okamoto Naika Clinic

Sapporo, Hokkaido, Japan

River Side Clinic

Sapporo, Hokkaido, Japan

Katsuya Iin

Amagasaki, Hyōgo, Japan

Kousei Hospital

Himeji, Hyōgo, Japan

Nakatani Hospital

Himeji, Hyōgo, Japan

Harima Clinic

Kakogawa, Hyōgo, Japan

Kusunose Surgery Clinic

Kobe, Hyōgo, Japan

Yamaki Medical Clinic

Hitachi-Naka, Ibaraki, Japan

Shika Clinic

Hakui, Ishikawa-ken, Japan

Yanagi Medical Clinic

Hakusan, Ishikawa-ken, Japan

Kakuda Iin

Kahoku, Ishikawa-ken, Japan

Dr Hayakawa's Family Clinic

Kanazawa, Ishikawa-ken, Japan

Wakasa Medical Clinic

Kanazawa, Ishikawa-ken, Japan

Okyozuka Clinic

Nonoichi, Ishikawa-ken, Japan

Matsuoka Clinic

Takamatsu, Kagawa-ken, Japan

Ori Clinic

Ashigarakami, Kanagawa, Japan

Iroden Clinic

Kamakura, Kanagawa, Japan

Nagasu Clinic

Kamakura, Kanagawa, Japan

Shohei Clinic

Kamakura, Kanagawa, Japan

Kamegaya Clinic

Kawasaki, Kanagawa, Japan

Kobayashi Hospital

Odawara, Kanagawa, Japan

Hakuai Iin

Sagamihara, Kanagawa, Japan

Yamamoto Clinic

Sagamihara, Kanagawa, Japan

International Goodwill Hospital

Yokohama, Kanagawa, Japan

Kikuchi Clinic

Yokohama, Kanagawa, Japan

Shimokurata Heart Clinic

Yokohama, Kanagawa, Japan

Tani Clinic Internal Medicine, Allergology & Rheumatology

Yokohama, Kanagawa, Japan

Tsurumi Chuo Clinic

Yokohama, Kanagawa, Japan

Yamagami Naika

Yokohama, Kanagawa, Japan

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan

Yokohama Sotetsu bldg Clinic of Internal Medicine

Yokohama, Kanagawa, Japan

Shimamoto Hospital

Kochi, Kochi, Japan

Toihata Naika

Aso, Kumamoto, Japan

Omori Iin

Kōshi, Kumamoto, Japan

Honjo Internal Medicine Hospital

Kumamoto, Kumamoto, Japan

Jinnouchi Clinic Diabetes Care Center

Kumamoto, Kumamoto, Japan

Kumamoto University Hospital

Kumamoto, Kumamoto, Japan

Maki Cardiovascular Clinic

Kumamoto, Kumamoto, Japan

Otsuka Hospital

Kumamoto, Kumamoto, Japan

Suizenji Touya Hospital

Kumamoto, Kumamoto, Japan

TERAO Hospital

Kumamoto, Kumamoto, Japan

Kan Kaimeido Clinic

Tamana, Kumamoto, Japan

Matsuo Clinic

Tamana, Kumamoto, Japan

Miyagi clinic cardiovascular medicine

Yatsushiro, Kumamoto, Japan

Isoda Internal Medical Clinic

Kyoto, Kyoto, Japan

Koseikai Clinic

Kyoto, Kyoto, Japan

Takenaka Clinic

Kyoto, Kyoto, Japan

Iwasaki Hospital

Tsu, Mie-ken, Japan

Yokota Naika

Miyazaki, Miyazaki, Japan

Eto Clinic

Nichinan, Miyazaki, Japan

Kawano Clinic

Nichinan, Miyazaki, Japan

Miyata Naika Iin

Nobeoka, Miyazaki, Japan

Nara Medical University Hospital

Kashihara, Nara, Japan

Ote Clinic of Internal

Sakurai, Nara, Japan

Uchiyama Clinic

Jōetsu, Niigata, Japan

Maeda Medical Clinic

Niigata, Niigata, Japan

Hospital, University of the Ryukyus

Nakagami, Okinawa, Japan

Nishimura Clinic

Fujiidera, Osaka, Japan

Ikeda Clinic

Higashiosaka, Osaka, Japan

Kanazawa Clinic

Izumi, Osaka, Japan

Akioka Clinic

Osaka, Osaka, Japan

Kinugawa Cardiology Clinic

Osaka, Osaka, Japan

Kondo Clinic

Osaka, Osaka, Japan

Kubota Clinic

Osaka, Osaka, Japan

Matsushita Medical Clinic

Osaka, Osaka, Japan

Nanko Clinic

Osaka, Osaka, Japan

Seo Heart Clinic

Osaka, Osaka, Japan

Watanabe Iin

Osaka, Osaka, Japan

Hayashi Medical Clinic

Sakai, Osaka, Japan

Matsuo Clinic

Yao, Osaka, Japan

Enomoto Clinic

Ageo, Saitama, Japan

Saitama Medical Center

Kawagoe, Saitama, Japan

Iryohojin Hogi sinryojyo

Kawaguchi, Saitama, Japan

Okuaki Clinic

Kawaguchi, Saitama, Japan

Tokutake Iin

Kawaguchi, Saitama, Japan

Medical Corporation Shibuya Clinic

Kumagaya, Saitama, Japan

Harada Medical Clinic

Shizuoka, Shizuoka, Japan

Shizuoka Municipal Hospital

Shizuoka, Shizuoka, Japan

Waki Riichiro Clinic

Shizuoka, Shizuoka, Japan

Ota Clinic

Awa, Tokushima, Japan

Minami National Health Insurance Hospital Of Minami Town

Kaifu-gun, Tokushima, Japan

Sekishinkan Hospital

Komatsushimachō, Tokushima, Japan

Tanaka Clinic

Myozai-gun, Tokushima, Japan

Itsumo Smile Clinic

Tokushima, Tokushima, Japan

Harada Clinic

Adachi-ku, Tokyo, Japan

Johoku Clinic

Adachi-ku, Tokyo, Japan

Moritani Clinic

Bunkyo-ku, Tokyo, Japan

Nishimura Memorial Hospital

Edogawa-ku, Tokyo, Japan

Hosoda-Clinic

Katsushika-ku, Tokyo, Japan

Okuda clinic

Kita-ku, Tokyo, Japan

Tenjinmae Clinic

Mitaka, Tokyo, Japan

Daiba Shinryojo

Nakano-ku, Tokyo, Japan

Kurumatani Clinic

Nerima-ku, Tokyo, Japan

Oono Iin

Nerima-ku, Tokyo, Japan

Sugawara Clinic

Nerima-ku, Tokyo, Japan

Baba Iin

Nishitōkyō, Tokyo, Japan

Miyahara Clinic

Ōta-ku, Tokyo, Japan

Taguchi Clinic

Shinagawa-ku, Tokyo, Japan

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo, Japan

Kobayashi Clinic

Suginami-ku, Tokyo, Japan

Tominaga Clinic

Tachikawa, Tokyo, Japan

Kirino Clinic

Toshima-ku, Tokyo, Japan

Yamada Clinic

Toshima-ku, Tokyo, Japan

Shimasaki Clinic

Yamagata, Yamagata, Japan

Ayame Medical Clinic

Shimonoseki, Yamaguchi, Japan

Matuda Clinic

Shimonoseki, Yamaguchi, Japan

Kuroda Iin

Ōtsuki, Yamanashi Pref., Japan

Countries

Japan

References

Sugawara M, Kojima S, Hisatome I, Matsui K, Uchiyama K, Yokota N, Tokutake E, Wakasa Y, Hiramitsu S, Waki M, Jinnouchi H, Kakuda H, Hayashi T, Kawai N, Mori H, Tsujita K, Ohya Y, Kimura K, Saito Y, Ogawa H; Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) investigators. Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial. Clin Pharmacol Ther. 2024 Jun;115(6):1358-1364. doi: 10.1002/cpt.3217. Epub 2024 Feb 23.

Reference Type: DERIVED

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Reference Type: DERIVED

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Kojima S, Matsui K, Hiramitsu S, Hisatome I, Waki M, Uchiyama K, Yokota N, Tokutake E, Wakasa Y, Jinnouchi H, Kakuda H, Hayashi T, Kawai N, Mori H, Sugawara M, Ohya Y, Kimura K, Saito Y, Ogawa H. Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy. Eur Heart J. 2019 Jun 7;40(22):1778-1786. doi: 10.1093/eurheartj/ehz119.

Reference Type: DERIVED

PMID: 30844048 (View on PubMed)

Kojima S, Matsui K, Ogawa H, Jinnouchi H, Hiramitsu S, Hayashi T, Yokota N, Kawai N, Tokutake E, Uchiyama K, Sugawara M, Kakuda H, Wakasa Y, Mori H, Hisatome I, Waki M, Ohya Y, Kimura K, Saito Y; Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study (FREED) investigators. Rationale, design, and baseline characteristics of a study to evaluate the effect of febuxostat in preventing cerebral, cardiovascular, and renal events in patients with hyperuricemia. J Cardiol. 2017 Jan;69(1):169-175. doi: 10.1016/j.jjcc.2016.02.015. Epub 2016 Apr 20.

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Other Identifiers

UMIN000012134

Identifier Type: REGISTRY

Identifier Source: secondary_id

0078

Identifier Type: -

Identifier Source: org_study_id