FREED: Febuxostat for Cerebral and caRdiorenovascular Events prEvEntion stuDy

Sponsor

Freed Study Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT01984749

Collaborator

Teijin Pharma Limited (Industry)

1,000

Enrollment

140

Locations

Arms

7.1

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperuricemia	Drug: Febuxostat	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Febuxostat treatment group Once daily after breakfast (generally within 30 minutes after eating)	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.
No Intervention: Non-febuxostat treatment group No febuxostat treatment

Arm

Intervention/Treatment

Experimental: Febuxostat treatment group

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

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.

No Intervention: Non-febuxostat treatment group

No febuxostat treatment

Outcome Measures

Primary Outcome Measures

Development of cerebral or cardiorenovascular events and all deaths [Enrollment through Month 36]
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

Secondary Outcome Measures

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]
Amount of change and percent change in serum uric acid level [Enrollment through Week 8]
Amount of change and percent change in serum uric acid level [Enrollment through Week 12]
Amount of change and percent change in serum uric acid level [Enrollment through Month 6]
Amount of change and percent change in serum uric acid level [Enrollment through Month 12]
Amount of change and percent change in serum uric acid level [Enrollment through Month 18]
Amount of change and percent change in serum uric acid level [Enrollment through Month 24]
Amount of change and percent change in serum uric acid level [Enrollment through Month 30]
Amount of change and percent change in serum uric acid level [Enrollment through Month 36 (or withdrawal from the study)]
Percent Achieving serum uric acid level of 6.0mg/dL [Enrollment to completion of study or withdrawal]
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)]
Amount of change and percent change in eGFR [Enrollment through Week 4]
Amount of change and percent change in eGFR [Enrollment through Week 8]
Amount of change and percent change in eGFR [Enrollment through Week 12]
Amount of change and percent change in eGFR [Enrollment through Month 6]
Amount of change and percent change in eGFR [Enrollment through Month 12]
Amount of change and percent change in eGFR [Enrollment through Month 18]
Amount of change and percent change in eGFR [Enrollment through Month 24]
Amount of change and percent change in eGFR [Enrollment through Month 30]
Amount of change and percent change in eGFR [Enrollment through Month 36 (or withdrawal from the study)]
Urine microalbumin-creatinine ratio [Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study)]
Amount of change and percent change in urine microalbumin-creatinine ratio [Enrollment through Month 6]
Amount of change and percent change in urine microalbumin-creatinine ratio [Enrollment through Month 12]
Amount of change and percent change in urine microalbumin-creatinine ratio [Enrollment through Month 24]
Amount of change and percent change in urine microalbumin-creatinine ratio [Enrollment through Month 36 (or withdrawal from the study)]
Quantification of urinary protein [Enrollment, 6, 12, 24, and 36 months (or withdrawal from the study)]
Amount of change and percent change in quantified urinary protein [Enrollment through Month 6]
Amount of change and percent change in quantified urinary protein [Enrollment through Month 12]
Amount of change and percent change in quantified urinary protein [Enrollment through Month 24]
Amount of change and percent change in quantitative urinary protein [Enrollment through Month 36 (or withdrawal from the study)]
Blood pressure (systolic/diastolic) [Enrollment, 6, 12, 18, 24, 30, and 36 months (or withdrawal from the study)]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 6]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 12]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 18]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 24]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 30]
Amount of change and percent change in blood pressure (systolic/diastolic) [Enrollment through Month 36 (or withdrawal from the study)]
Occurrence of adverse events [Enrollment through Month 36]
Occurrence of cerebral or cardiorenovascular events in the febuxostat group during the study period by febuxostat dose [Enrollment through Month 36]
Occurrence of cerebral or cardiorenovascular events in the non-febuxostat group during the study period by use of allopurinol [Enrollment through Month 36]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hiramitsu Heart Clinic	Nagoya	Aichi	Japan
2	Ogawa-naika Clinic	Nagoya	Aichi	Japan
3	Shakaiiryohoｊin Koｊunkai Daido Hospital	Nagoya	Aichi	Japan
4	Honjo Daiichi Hospital	Yurihonjo	Akita	Japan
5	Iriyouhoujin Siyadan Yanagisawakai Yanagisawaiin	Matsudo	Chiba	Japan
6	Matsuno Medical Clinic	Iyo-gun	Ehime	Japan
7	Ishite Matsumoto Naika Junkanki Clinic	Matsuyama	Ehime	Japan
8	Ehime Medical CO-OP Izumigawa Clinic	Niihama	Ehime	Japan
9	Hanaoka IC Clinic	Buzen	Fukuoka	Japan
10	Otonari Clinic	Chikushino	Fukuoka	Japan
11	Medical Cooperation Toseikai Goto Clinic	Kitakyushu	Fukuoka	Japan
12	ONGA NAKAMA Medical Association ONGA Hospital	Onga-gun	Fukuoka	Japan
13	Southern Tohoku Research Institute For Neuroscience Southern Tohoku Medical Clinic	Koriyama	Fukushima	Japan
14	Noda Clinic	Ibi	Gifu	Japan
15	Sunomata Clinic	Ogaki	Gifu	Japan
16	Tsurugaya Hospital	Isesaki	Gunma	Japan
17	Nakano Clinic	Shibukawa	Gunma	Japan
18	Iryouhoujinn Makikai Makibyouinn	Takasaki	Gunma	Japan
19	Shigenobu Clinic	Miyoshi	Hiroshima	Japan
20	Keiyukai Yoshida Hospital	Asahikawa	Hokkaido	Japan
21	Matsui Naika Clinic	Asahikawa	Hokkaido	Japan
22	Omiya Clinic	Asahikawa	Hokkaido	Japan
23	Miyanomori Memorial Hospital	Sapporo	Hokkaido	Japan
24	Okamoto Naika Clinic	Sapporo	Hokkaido	Japan
25	River Side Clinic	Sapporo	Hokkaido	Japan
26	Katsuya Iin	Amagasaki	Hyogo	Japan
27	Kousei Hospital	Himeji	Hyogo	Japan
28	Nakatani Hospital	Himeji	Hyogo	Japan
29	Harima Clinic	Kakogawa	Hyogo	Japan
30	Kusunose Surgery Clinic	Kobe	Hyogo	Japan
31	Yamaki Medical Clinic	Hitachinaka	Ibaraki	Japan
32	Shika Clinic	Hakui	Ishikawa	Japan
33	Yanagi Medical Clinic	Hakusan	Ishikawa	Japan
34	Kakuda Iin	Kahoku	Ishikawa	Japan
35	Dr Hayakawa's Family Clinic	Kanazawa	Ishikawa	Japan
36	Wakasa Medical Clinic	Kanazawa	Ishikawa	Japan
37	Okyozuka Clinic	Nonoichi	Ishikawa	Japan
38	Matsuoka Clinic	Takamatsu	Kagawa	Japan
39	Ori Clinic	Ashigarakami	Kanagawa	Japan
40	Iroden Clinic	Kamakura	Kanagawa	Japan
41	Nagasu Clinic	Kamakura	Kanagawa	Japan
42	Shohei Clinic	Kamakura	Kanagawa	Japan
43	Kamegaya Clinic	Kawasaki	Kanagawa	Japan
44	Kobayashi Hospital	Odawara	Kanagawa	Japan
45	Hakuai Iin	Sagamihara	Kanagawa	Japan
46	Yamamoto Clinic	Sagamihara	Kanagawa	Japan
47	International Goodwill Hospital	Yokohama	Kanagawa	Japan
48	Kikuchi Clinic	Yokohama	Kanagawa	Japan
49	Shimokurata Heart Clinic	Yokohama	Kanagawa	Japan
50	Tani Clinic Internal Medicine, Allergology & Rheumatology	Yokohama	Kanagawa	Japan
51	Tsurumi Chuo Clinic	Yokohama	Kanagawa	Japan
52	Yamagami Naika	Yokohama	Kanagawa	Japan
53	Yokohama City University Medical Center	Yokohama	Kanagawa	Japan
54	Yokohama Sotetsu bldg Clinic of Internal Medicine	Yokohama	Kanagawa	Japan
55	Toihata Naika	Aso	Kumamoto	Japan
56	Omori Iin	Koshi	Kumamoto	Japan
57	Kan Kaimeido Clinic	Tamana	Kumamoto	Japan
58	Matsuo Clinic	Tamana	Kumamoto	Japan
59	Miyagi clinic cardiovascular medicine	Yatsushiro	Kumamoto	Japan
60	Iwasaki Hospital	Tsu	Mie	Japan
61	Eto Clinic	Nichinan	Miyazaki	Japan
62	Kawano Clinic	Nichinan	Miyazaki	Japan
63	Miyata Naika Iin	Nobeoka	Miyazaki	Japan
64	Nara Medical University Hospital	Kashihara	Nara	Japan
65	Ote Clinic of Internal	Sakurai	Nara	Japan
66	Uchiyama Clinic	Joetsu	Niigata	Japan
67	Hospital, University of the Ryukyus	Nakagami	Okinawa	Japan
68	Nishimura Clinic	Fujiidera	Osaka	Japan
69	Ikeda Clinic	Higashiosaka	Osaka	Japan
70	Kanazawa Clinic	Izumi	Osaka	Japan
71	Hayashi Medical Clinic	Sakai	Osaka	Japan
72	Matsuo Clinic	Yao	Osaka	Japan
73	Enomoto Clinic	Ageo	Saitama	Japan
74	Saitama Medical Center	Kawagoe	Saitama	Japan
75	Iryohojin Hogi sinryojyo	Kawaguchi	Saitama	Japan
76	Okuaki Clinic	Kawaguchi	Saitama	Japan
77	Tokutake Iin	Kawaguchi	Saitama	Japan
78	Medical Corporation Shibuya Clinic	Kumagaya	Saitama	Japan
79	Ota Clinic	Awa	Tokushima	Japan
80	Minami National Health Insurance Hospital Of Minami Town	Kaifu-gun	Tokushima	Japan
81	Sekishinkan Hospital	Komatsushima	Tokushima	Japan
82	Tanaka Clinic	Myozai-gun	Tokushima	Japan
83	Harada Clinic	Adachi-ku	Tokyo	Japan
84	Johoku Clinic	Adachi-ku	Tokyo	Japan
85	Moritani Clinic	Bunkyo-ku	Tokyo	Japan
86	Nishimura Memorial Hospital	Edogawa-ku	Tokyo	Japan
87	Hosoda-Clinic	Katsushika-ku	Tokyo	Japan
88	Okuda clinic	Kita-ku	Tokyo	Japan
89	Tenjinmae Clinic	Mitaka	Tokyo	Japan
90	Daiba Shinryojo	Nakano-ku	Tokyo	Japan
91	Kurumatani Clinic	Nerima-ku	Tokyo	Japan
92	Oono Iin	Nerima-ku	Tokyo	Japan
93	Sugawara Clinic	Nerima-ku	Tokyo	Japan
94	Baba Iin	Nishitokyo	Tokyo	Japan
95	Miyahara Clinic	Ota-ku	Tokyo	Japan
96	Taguchi Clinic	Shinagawa-ku	Tokyo	Japan
97	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo	Japan
98	Kobayashi Clinic	Suginami-ku	Tokyo	Japan
99	Tominaga Clinic	Tachikawa	Tokyo	Japan
100	Kirino Clinic	Toshima-ku	Tokyo	Japan
101	Yamada Clinic	Toshima-ku	Tokyo	Japan
102	Ayame Medical Clinic	Shimonoseki	Yamaguchi	Japan
103	Matuda Clinic	Shimonoseki	Yamaguchi	Japan
104	Kuroda Iin	Otsuki city	Yamanashi pref.	Japan	409-0614
105	Saku Hospital	Fukuoka		Japan
106	Tohaya Iin	Fukuoka		Japan
107	Iryohojin Shadan Seijinkai Kawade Iin	Gifu		Japan
108	Kawai Naika Clinic	Gifu		Japan
109	Miwa Clinic: Gastroenterology Hepatology	Gifu		Japan
110	Sagou Clinic	Gifu		Japan
111	Sasaki Clinic	Gifu		Japan
112	Takai Clinic	Gifu		Japan
113	Takeda Clinic	Gifu		Japan
114	Totani Medical Clinic	Gifu		Japan
115	Shimamoto Hospital	Kochi		Japan
116	Honjo Internal Medicine Hospital	Kumamoto		Japan
117	Jinnouchi Clinic Diabetes Care Center	Kumamoto		Japan
118	Kumamoto University Hospital	Kumamoto		Japan
119	Maki Cardiovascular Clinic	Kumamoto		Japan
120	Otsuka Hospital	Kumamoto		Japan
121	Suizenji Touya Hospital	Kumamoto		Japan
122	TERAO Hospital	Kumamoto		Japan
123	Isoda Internal Medical Clinic	Kyoto		Japan
124	Koseikai Clinic	Kyoto		Japan
125	Takenaka Clinic	Kyoto		Japan
126	Yokota Naika	Miyazaki		Japan
127	Maeda Medical Clinic	Niigata		Japan
128	Akioka Clinic	Osaka		Japan
129	Kinugawa Cardiology Clinic	Osaka		Japan
130	Kondo Clinic	Osaka		Japan
131	Kubota Clinic	Osaka		Japan
132	Matsushita Medical Clinic	Osaka		Japan
133	Nanko Clinic	Osaka		Japan
134	Seo Heart Clinic	Osaka		Japan
135	Watanabe Iin	Osaka		Japan
136	Harada Medical Clinic	Shizuoka		Japan
137	Shizuoka Municipal Hospital	Shizuoka		Japan
138	Waki Riichiro Clinic	Shizuoka		Japan
139	Itsumo Smile Clinic	Tokushima		Japan
140	Shimasaki Clinic	Yamagata		Japan

Sponsors and Collaborators

Freed Study Group
Teijin Pharma Limited

Investigators

Study Chair: Hisao Ogawa, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hisao Ogawa, Deputy Director General of the hospital, National Cerebral and Cardiovascular Center Hospital, Freed Study Group

ClinicalTrials.gov Identifier:

NCT01984749

Other Study ID Numbers:

0078
UMIN000012134

First Posted:

Nov 15, 2013

Last Update Posted:

Aug 26, 2016

Last Verified:

Aug 1, 2016

Additional relevant MeSH terms:

Hyperuricemia

Febuxostat

Study Results

No Results Posted as of Aug 26, 2016