UMIN-CTR Clinical Trial

Basic information
Public title	Program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled study (PRIZE) sub study
Acronym	Program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled study (PRIZE) sub study
Scientific Title	Program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled study (PRIZE) sub study
Scientific Title:Acronym	Program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled study (PRIZE) sub study
Region	Japan

Condition
Condition	The analysis data set of the main trial will be used as the database of this study.
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To examine in greater detail the protective effect of febuxostat against vascular damage by patient background and pathology, and to elucidate from various perspectives the efficacy and safety of febuxostat when used for the treatment of hyperuricemia through examination of organ-related effects of febuxostat and the relationship with other clinical indicators obtained in this study, by conducting the sub-studies (as described below) of the program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled study (hereinafter referred to as main trial), which was conducted from January 2014 through March 2019. Specifically, in the sub-studies, the impact of febuxostat on flow-mediated dilation (FMD), pulse wave velocity (PWV), the cardio ankle vascular index (CAVI), IMT, echocardiography, etc., as well as the relationship between febuxostat and other clinical indicators (uric acid level, etc.) will be evaluated. In addition, the impact of febuxostat on exploratory biomarkers, etc., associated with the remodeling of cardiac and renal disorders and the progression of dysfunction, the efficacy and safety of febuxostat in patients with chronic kidney disease (CKD), and the impact of fluctuations in blood pressure on the progression of arteriosclerosis will be examined. Moreover, a more detailed stratified analysis will be conducted by clinical setting and administered dose of febuxostat, and by using such indicators as the uric acid level. By doing these, the efficacy and safety of febuxostat regarding various clinical indicators such as carotid IMT and uric acid level-that have not been analyzed in detail yet although data on these have already been obtained at the main trial-will be analyzed, with the goal of elucidating the effect of febuxostat on hyperuricemia from various perspectives.
Basic objectives2	Others
Basic objectives -Others	Examination of the impact of febuxostat on FMD,carotid plaque echolucency, IMT,cardiac function,hepatic function, MDA-LDL ,kidneys,biomarkers, and lipids. Examination for the elucidation of carotid IMT progression factors.Examination of the impact of fluctuations in blood pressure on the progression of arteriosclerosis.Examination of the impact of febuxostat on vascular functions hardness of arteries based on blood-pressure levels and the presence or absence of hypertension and renal impairment.Examination of the impact of febuxostat on carotid IMT based on vascular functions.Examination of the relationship between uric acid and vascular function/ sRAGE.Examination of the impact on carotid IMT by febuxostat dose.Examination of the impact on carotid IMT by uric acid level.Examination of predictive factors of MACE.Examination of the quality of trial data obtained in multicenter studies.
Trial characteristics_1
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	Rate of change from baseline after 24 months in the mean IMT value of the common carotid artery determined by carotid artery ultrasound
Key secondary outcomes	1. IMT, FMD, PWV, CAVI, EF, LVEF, E, A, TRPG, e' and E/e' by treatment group at each measurement point 2. Blood test values (red blood cells, white blood cells, hemoglobin, hematocrit, blood platelet count, AST, ALT, LDH, BUN, Na, K, Cl, blood glucose, serum uric acid level, serum lipids: TC, HDL-C, TG, non-HDL-C, LDL-C, serum creatinine, eGFR), serum biomarker values NT-proBNP, high-sensitivity CRP, 1, 5AG, small dense LDL, RLP-C, MDA-LDL, serum cystatin C, RAGE, high-molecular adiponectin, high-sensitivity troponin I, ANGPTL2, Alb, Ca, FGF23, P), and urine test values (urinary albumin excretion, urinary L-FABP) by treatment group at each measurement point

Base
Study type	Others,meta-analysis etc

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	The analysis data set of the main trial will be used as the database of this study. Number of cases in the database: Febuxostat group: 239 cases Control group: 244 cases
Key exclusion criteria	Not applicable
Target sample size	483

Research contact person
Name of lead principal investigator	1st name Koichi Middle name Last name Node
Organization	Saga University
Division name	Department of Cardiovascular Medicine
Zip code	849-8501
Address	5-1-1 Nabeshima, Saga
TEL	0952-34-2364
Email	cardiostudy@ml.cc.saga-u.ac.jp

Public contact
Name of contact person	1st name Atsushi Middle name Last name Tanaka
Organization	Saga University
Division name	Department of Cardiovascular Medicine
Zip code	849-8501
Address	5-1-1 Nabeshima, Saga
TEL	0952-34-2364
Homepage URL
Email	cardiostudy@ml.cc.saga-u.ac.jp

Sponsor
Institute	Department of Cardiovascular Medicine, Saga University
Institute
Department

Funding Source
Organization	TEIJIN PHARMA LIMITED
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Clinical Research Center,Saga University Hospital
Address	5-1-1 Nabeshima, Saga
Tel	0952-34-3400
Email	kenkyu-shinsei@ml.cc.saga-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	佐賀大学

Other administrative information
Date of disclosure of the study information	2020 Year 08 Month 10 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications
Number of participants that the trial has enrolled	483
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2020 Year 05 Month 26 Day
Date of IRB	2020 Year 07 Month 22 Day
Anticipated trial start date	2020 Year 08 Month 04 Day
Last follow-up date	2021 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	The analysis data set that was obtained in the main trial will be used as the database of this study. Program of vascular evaluation under uric acid control by xanthine oxidase inhibitor , febuxostat : multicenter , randomized controlled study

Management information
Registered date	2020 Year 08 Month 05 Day
Last modified on	2022 Year 08 Month 25 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047173