Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy

Hyperuricemia Clinical Trial

— FREED  

Official title:

A Multicenter, Randomized, Comparative Trial on the Effect of Febuxostat in Preventing Cerebral and Cardiorenovascular Events in Patients With Hyperuricemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01984749
• Other study ID #: 0078
• Secondary ID: UMIN000012134
• Status: Active, not recruiting
• Phase: N/A
• First received: October 30, 2013
• Last updated: August 25, 2016
• Start date: November 2013

Study information

• Verified date: August 2016
• Source: Freed Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperuricemia

Intervention

Drug:
• 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. The starting dose of the investigational product (febuxostat) will be 10 mg/day. The dose will be increased to 20 mg/day at Week 4. The aim is to increase the dose to 40 mg/day at Week 8.

Locations

Country	Name	City	State
Japan	Harada Clinic	Adachi-ku	Tokyo
Japan	Johoku Clinic	Adachi-ku	Tokyo
Japan	Enomoto Clinic	Ageo	Saitama
Japan	Katsuya Iin	Amagasaki	Hyogo
Japan	Keiyukai Yoshida Hospital	Asahikawa	Hokkaido
Japan	Matsui Naika Clinic	Asahikawa	Hokkaido
Japan	Omiya Clinic	Asahikawa	Hokkaido
Japan	Ori Clinic	Ashigarakami	Kanagawa
Japan	Toihata Naika	Aso	Kumamoto
Japan	Ota Clinic	Awa	Tokushima
Japan	Moritani Clinic	Bunkyo-ku	Tokyo
Japan	Hanaoka IC Clinic	Buzen	Fukuoka
Japan	Otonari Clinic	Chikushino	Fukuoka
Japan	Nishimura Memorial Hospital	Edogawa-ku	Tokyo
Japan	Nishimura Clinic	Fujiidera	Osaka
Japan	Saku Hospital	Fukuoka
Japan	Tohaya Iin	Fukuoka
Japan	Iryohojin Shadan Seijinkai Kawade Iin	Gifu
Japan	Kawai Naika Clinic	Gifu
Japan	Miwa Clinic: Gastroenterology Hepatology	Gifu
Japan	Sagou Clinic	Gifu
Japan	Sasaki Clinic	Gifu
Japan	Takai Clinic	Gifu
Japan	Takeda Clinic	Gifu
Japan	Totani Medical Clinic	Gifu
Japan	Shika Clinic	Hakui	Ishikawa
Japan	Yanagi Medical Clinic	Hakusan	Ishikawa
Japan	Ikeda Clinic	Higashiosaka	Osaka
Japan	Kousei Hospital	Himeji	Hyogo
Japan	Nakatani Hospital	Himeji	Hyogo
Japan	Yamaki Medical Clinic	Hitachinaka	Ibaraki
Japan	Noda Clinic	Ibi	Gifu
Japan	Tsurugaya Hospital	Isesaki	Gunma
Japan	Matsuno Medical Clinic	Iyo-gun	Ehime
Japan	Kanazawa Clinic	Izumi	Osaka
Japan	Uchiyama Clinic	Joetsu	Niigata
Japan	Kakuda Iin	Kahoku	Ishikawa
Japan	Minami National Health Insurance Hospital Of Minami Town	Kaifu-gun	Tokushima
Japan	Harima Clinic	Kakogawa	Hyogo
Japan	Iroden Clinic	Kamakura	Kanagawa
Japan	Nagasu Clinic	Kamakura	Kanagawa
Japan	Shohei Clinic	Kamakura	Kanagawa
Japan	Dr Hayakawa's Family Clinic	Kanazawa	Ishikawa
Japan	Wakasa Medical Clinic	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	Hosoda-Clinic	Katsushika-ku	Tokyo
Japan	Saitama Medical Center	Kawagoe	Saitama
Japan	Iryohojin Hogi sinryojyo	Kawaguchi	Saitama
Japan	Okuaki Clinic	Kawaguchi	Saitama
Japan	Tokutake Iin	Kawaguchi	Saitama
Japan	Kamegaya Clinic	Kawasaki	Kanagawa
Japan	Okuda clinic	Kita-ku	Tokyo
Japan	Medical Cooperation Toseikai Goto Clinic	Kitakyushu	Fukuoka
Japan	Kusunose Surgery Clinic	Kobe	Hyogo
Japan	Shimamoto Hospital	Kochi
Japan	Sekishinkan Hospital	Komatsushima	Tokushima
Japan	Southern Tohoku Research Institute For Neuroscience Southern Tohoku Medical Clinic	Koriyama	Fukushima
Japan	Omori Iin	Koshi	Kumamoto
Japan	Medical Corporation Shibuya Clinic	Kumagaya	Saitama
Japan	Honjo Internal Medicine Hospital	Kumamoto
Japan	Jinnouchi Clinic Diabetes Care Center	Kumamoto
Japan	Kumamoto University Hospital	Kumamoto
Japan	Maki Cardiovascular Clinic	Kumamoto
Japan	Otsuka Hospital	Kumamoto
Japan	Suizenji Touya Hospital	Kumamoto
Japan	TERAO Hospital	Kumamoto
Japan	Isoda Internal Medical Clinic	Kyoto
Japan	Koseikai Clinic	Kyoto
Japan	Takenaka Clinic	Kyoto
Japan	Iriyouhoujin Siyadan Yanagisawakai Yanagisawaiin	Matsudo	Chiba
Japan	Ishite Matsumoto Naika Junkanki Clinic	Matsuyama	Ehime
Japan	Tenjinmae Clinic	Mitaka	Tokyo
Japan	Yokota Naika	Miyazaki
Japan	Shigenobu Clinic	Miyoshi	Hiroshima
Japan	Tanaka Clinic	Myozai-gun	Tokushima
Japan	Hiramitsu Heart Clinic	Nagoya	Aichi
Japan	Ogawa-naika Clinic	Nagoya	Aichi
Japan	Shakaiiryohojin Kojunkai Daido Hospital	Nagoya	Aichi
Japan	Hospital, University of the Ryukyus	Nakagami	Okinawa
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	Eto Clinic	Nichinan	Miyazaki
Japan	Kawano Clinic	Nichinan	Miyazaki
Japan	Maeda Medical Clinic	Niigata
Japan	Ehime Medical CO-OP Izumigawa Clinic	Niihama	Ehime
Japan	Baba Iin	Nishitokyo	Tokyo
Japan	Miyata Naika Iin	Nobeoka	Miyazaki
Japan	Okyozuka Clinic	Nonoichi	Ishikawa
Japan	Kobayashi Hospital	Odawara	Kanagawa
Japan	Sunomata Clinic	Ogaki	Gifu
Japan	ONGA NAKAMA Medical Association ONGA Hospital	Onga-gun	Fukuoka
Japan	Akioka Clinic	Osaka
Japan	Kinugawa Cardiology Clinic	Osaka
Japan	Kondo Clinic	Osaka
Japan	Kubota Clinic	Osaka
Japan	Matsushita Medical Clinic	Osaka
Japan	Nanko Clinic	Osaka
Japan	Seo Heart Clinic	Osaka
Japan	Watanabe Iin	Osaka
Japan	Miyahara Clinic	Ota-ku	Tokyo
Japan	Kuroda Iin	Otsuki city	Yamanashi pref.
Japan	Hakuai Iin	Sagamihara	Kanagawa
Japan	Yamamoto Clinic	Sagamihara	Kanagawa
Japan	Hayashi Medical Clinic	Sakai	Osaka
Japan	Ote Clinic of Internal	Sakurai	Nara
Japan	Miyanomori Memorial Hospital	Sapporo	Hokkaido
Japan	Okamoto Naika Clinic	Sapporo	Hokkaido
Japan	River Side Clinic	Sapporo	Hokkaido
Japan	Nakano Clinic	Shibukawa	Gunma
Japan	Ayame Medical Clinic	Shimonoseki	Yamaguchi
Japan	Matuda Clinic	Shimonoseki	Yamaguchi
Japan	Taguchi Clinic	Shinagawa-ku	Tokyo
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Harada Medical Clinic	Shizuoka
Japan	Shizuoka Municipal Hospital	Shizuoka
Japan	Waki Riichiro Clinic	Shizuoka
Japan	Kobayashi Clinic	Suginami-ku	Tokyo
Japan	Tominaga Clinic	Tachikawa	Tokyo
Japan	Matsuoka Clinic	Takamatsu	Kagawa
Japan	Iryouhoujinn Makikai Makibyouinn	Takasaki	Gunma
Japan	Kan Kaimeido Clinic	Tamana	Kumamoto
Japan	Matsuo Clinic	Tamana	Kumamoto
Japan	Itsumo Smile Clinic	Tokushima
Japan	Kirino Clinic	Toshima-ku	Tokyo
Japan	Yamada Clinic	Toshima-ku	Tokyo
Japan	Iwasaki Hospital	Tsu	Mie
Japan	Shimasaki Clinic	Yamagata
Japan	Matsuo Clinic	Yao	Osaka
Japan	Miyagi clinic cardiovascular medicine	Yatsushiro	Kumamoto
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	Honjo Daiichi Hospital	Yurihonjo	Akita

Sponsors (2)

Lead Sponsor	Collaborator
Freed Study Group	Teijin Pharma

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of cerebral or cardiorenovascular events and all deaths	Definition of "cerebral and cardiorenovascular events": Death due to cerebral or cardiorenovascular disease; New or recurrent cerebrovascular disease (stroke [cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, stroke of unknown type], transient ischemic attack; New or recurrent non-fatal coronary artery disease (myocardial infarction and unstable angina pectoris); Cardiac failure requiring hospitalization; Arteriosclerotic disease requiring hospitalization (aortic aneurysm, aortic dissection, and arteriosclerosis obliterans); 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); New atrial fibrillation (including paroxysmal atrial fibrillation); Deaths that are not caused by cerebral or cardiorenovascular disease	Enrollment through Month 36	Yes
Secondary	Occurrence of cerebral or cardiorenovascular event by event		Enrollment through Month 36	Yes
Secondary	Occurrence of cerebral or cardiorenovascular event by serum uric acid level		Enrollment through Month 36	Yes
Secondary	Occurrence of cerebral or cardiorenovascular event by prior history of cerebral or cardiorenovascular disease		Enrollment through Month 36	Yes
Secondary	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)	Yes
Secondary	Change in serum uric acid level		Enrollment through Week 4	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Week 8	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Week 12	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 6	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 12	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 18	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 24	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 30	Yes
Secondary	Amount of change and percent change in serum uric acid level		Enrollment through Month 36 (or withdrawal from the study)	Yes
Secondary	Percent Achieving serum uric acid level of 6.0mg/dL		Enrollment to completion of study or withdrawal	Yes
Secondary	Estimated glomerular filtration rate (eGFR)		Enrollment, 4, 8, and 12 weeks and 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study)	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Week 4	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Week 8	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Week 12	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 6	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 12	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 18	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 24	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 30	Yes
Secondary	Amount of change and percent change in eGFR		Enrollment through Month 36 (or withdrawal from the study)	Yes
Secondary	Urine microalbumin-creatinine ratio		Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study)	Yes
Secondary	Amount of change and percent change in urine microalbumin-creatinine ratio		Enrollment through Month 6	Yes
Secondary	Amount of change and percent change in urine microalbumin-creatinine ratio		Enrollment through Month 12	Yes
Secondary	Amount of change and percent change in urine microalbumin-creatinine ratio		Enrollment through Month 24	Yes
Secondary	Amount of change and percent change in urine microalbumin-creatinine ratio		Enrollment through Month 36 (or withdrawal from the study)	Yes
Secondary	Quantification of urinary protein		Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study)	Yes
Secondary	Amount of change and percent change in quantified urinary protein		Enrollment through Month 6	Yes
Secondary	Amount of change and percent change in quantified urinary protein		Enrollment through Month 12	Yes
Secondary	Amount of change and percent change in quantified urinary protein		Enrollment through Month 24	Yes
Secondary	Amount of change and percent change in quantitative urinary protein		Enrollment through Month 36 (or withdrawal from the study)	Yes
Secondary	Blood pressure (systolic/diastolic)		Enrollment, 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study)	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 6	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 12	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 18	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 24	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 30	Yes
Secondary	Amount of change and percent change in blood pressure (systolic/diastolic)		Enrollment through Month 36 (or withdrawal from the study)	Yes
Secondary	Occurrence of adverse events		Enrollment through Month 36	Yes
Secondary	Occurrence of cerebral or cardiorenovascular events in the febuxostat group during the study period by febuxostat dose		Enrollment through Month 36	Yes
Secondary	Occurrence of cerebral or cardiorenovascular events in the non-febuxostat group during the study period by use of allopurinol		Enrollment through Month 36	Yes