Febuxostat for Cerebral and caRdiorenovascular Events prE... | NCT01984749

ID	Type	Description	Link
UMIN000012134	Registry Identifier	UMIN

Status Module

Name	Class
Teijin Pharma Limited	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Febuxostat treatment group	Experimental	Once daily after breakfast (generally within 30 minutes after eating)	Drug: Febuxostat
Non-febuxostat treatment group	No Intervention	No febuxostat treatment

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Febuxostat	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. 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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
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

Eligibility Module

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

Name	Affiliation	Role
Hisao Ogawa	Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Hiramitsu Heart Clinic		Nagoya	Aichi-ken		Japan
Ogawa-naika Clinic

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38389505	Derived	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.
35648242

Type	Date	Date Unknown
Release	Apr 14, 2019
Reset	Jul 2, 2019
Release	Jul 28, 2019

Release Date	Unrelease Date	Unrelease Date Unknown	Reset Date	MCP Release Number
Apr 14, 2019			Jul 2, 2019
Jul 28, 2019			Sep 6, 2019
Feb 21, 2024			Aug 5, 2024

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013844	Thiazoles
D013457	Sulfur Compounds
D009930	Organic Chemicals
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds