Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy
FREED
A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia
2 other identifiers
interventional
1,000
1 country
140
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
140 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2013
CompletedStudy Start
First participant enrolled
November 1, 2013
CompletedFirst Posted
Study publicly available on registry
November 15, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2017
CompletedAugust 26, 2016
August 1, 2016
3.9 years
October 30, 2013
August 25, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Development of cerebral or cardiorenovascular events and all deaths
Definition of "cerebral and cardiorenovascular events": 1. Death due to cerebral or cardiorenovascular disease 2. New or recurrent cerebrovascular disease (stroke \[cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, stroke of unknown type\], transient ischemic attack 3. New or recurrent non-fatal coronary artery disease (myocardial infarction and unstable angina pectoris) 4. Cardiac failure requiring hospitalization 5. Arteriosclerotic disease requiring hospitalization (aortic aneurysm, aortic dissection, and arteriosclerosis obliterans) 6. Renal impairment (development of microalbuminuria, progression to overt proteinuria, or overt proteinuria \[≥ 300 mg/gCr\], confirmed by two consecutive laboratory tests performed after the initiation of study treatments; doubling of serum creatinine level; and progression to ESRD) 7. New atrial fibrillation (including paroxysmal atrial fibrillation) 8. Deaths that are not caused by cerebral or cardiorenovascular disease
Enrollment through Month 36
Secondary Outcomes (44)
Occurrence of cerebral or cardiorenovascular event by event
Enrollment through Month 36
Occurrence of cerebral or cardiorenovascular event by serum uric acid level
Enrollment through Month 36
Occurrence of cerebral or cardiorenovascular event by prior history of cerebral or cardiorenovascular disease
Enrollment through Month 36
Serum uric acid level
At screening, at enrollment, at 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or at withdrawal from the study)
Change in serum uric acid level
Enrollment through Week 4
- +39 more secondary outcomes
Study Arms (2)
Febuxostat treatment group
EXPERIMENTALOnce daily after breakfast (generally within 30 minutes after eating)
Non-febuxostat treatment group
NO INTERVENTIONNo febuxostat treatment
Interventions
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.
Eligibility Criteria
You may qualify if:
- (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
You may not qualify if:
- (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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Freed Study Grouplead
- Teijin Pharma Limitedcollaborator
Study Sites (140)
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., 409-0614, Japan
Related Publications (5)
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.
PMID: 38389505DERIVEDKojima S, Uchiyama K, Yokota N, Tokutake E, Wakasa Y, Hiramitsu S, Waki M, Jinnouchi H, Kakuda H, Hayashi T, Kawai N, Sugawara M, Mori H, Tsujita K, Matsui K, Hisatome I, Ohya Y, Kimura K, Saito Y, Ogawa H; Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) investigators. C-reactive Protein Levels and Cardiovascular Outcomes After Febuxostat Treatment in Patients with Asymptomatic Hyperuricemia: Post-hoc Analysis of a Randomized Controlled Study. Cardiovasc Drugs Ther. 2023 Oct;37(5):965-974. doi: 10.1007/s10557-022-07347-7. Epub 2022 Jun 1.
PMID: 35648242DERIVEDKojima S, Uchiyama K, Yokota N, Tokutake E, Wakasa Y, Hiramitsu S, Waki M, Jinnouchi H, Kakuda H, Hayashi T, Kawai N, Sugawara M, Mori H, Tsujita K, Matsui K, Hisatome I, Ohya Y, Kimura K, Saito Y, Ogawa H; Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study (FREED) investigators. Optimal uric acid levels by febuxostat treatment and cerebral, cardiorenovascular risks: post hoc analysis of a randomized controlled trial. Rheumatology (Oxford). 2022 May 30;61(6):2346-2359. doi: 10.1093/rheumatology/keab739.
PMID: 34605897DERIVEDKojima 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.
PMID: 30844048DERIVEDKojima 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.
PMID: 27005768DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Hisao Ogawa
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Deputy Director General of the hospital, National Cerebral and Cardiovascular Center Hospital
Study Record Dates
First Submitted
October 30, 2013
First Posted
November 15, 2013
Study Start
November 1, 2013
Primary Completion
October 1, 2017
Last Updated
August 26, 2016
Record last verified: 2016-08