UMIN-CTR Clinical Trial

Public title

The Effect of Febuxostat on the Patient with Hyperuricemia and Non-alcoholic Steatohepatitis

Acronym

Hyperuricemia and Non-alcoholic Steatohepatitis

Scientific Title

The Effect of Febuxostat on the Patient with Hyperuricemia and Non-alcoholic Steatohepatitis

Scientific Title:Acronym

Hyperuricemia and Non-alcoholic Steatohepatitis

Region

Japan

Condition

Hyperuricemia and Non-Alcoholic Steatohepatitis

Classification by specialty

Hepato-biliary-pancreatic medicine

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

Several epidemiological studies have suggested that hyperuricemia is one of the causes of Non-alcoholic steatohepatitis (NASH) or related to the progression of NASH. However, no prospective studies have been done to test the effect of treatment of hyperuricemia on NASH. Thus, the aim of this study is to test the efficiency and safety of Febuxostat, one of uric acid-lowering agent, on the patient with hyperuricemia and NASH and clarify the role of hypeuricemia on NASH.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I,II

Primary outcomes

Improvement of serum ALT after taking Febuxostat for 6 months

Key secondary outcomes

The following are assessed after taking Febuxostat for 6 months;
1. Safety
2. Improvement of fatty liver by CT
3. Improvement of histological findings of liver
4. The effect of Febuxostat on serum uric acid, liver function except for ALT, renal function, lipid and glucose metabolism, cytokines, and oxidative-stress marker.
5. The effect of Febuxostat on the gene expression related to uric metabolism and glucose metabolism in blood and liver

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Febuxostat 10mg per day will be given to the patients as the first dose, and then it can be increased to 20mg and 40mg per day every 4 week. The maintenance dose should be 40mg per day, however, it can be increased up to 60mg depend on the status of the patients. It should be taken once a day, every morning.

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

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Serum uric acid; more than 7.0 mg/dl
2. Diagnosed as NASH by imaging studies or histological test(The histological test should be done within 5 years before entry of this study.)
3. Serum ALT; greater than or equal to 31 IU/L
4. Tolerable to take Febuxostat for at least 6 months
5. Child-Pugh classification A
6. Age older than or equal to 20 years old at the entry
7. Performance status (ECOG scale) 0 or 1
8. The function of main organs should be well maintained within 30 days before entry.
1. WBC; greater than or equal to 3000 and less than 12000 /ul
2. Hb; greater than or equal to 9.0g/dL
3. Platelet; greater than or equal to 70000 /ul
4. Total Bilirubin; less than or equal to 1.5 mg/dL or lower than upper limit of the clinic
5. Serum Cr; less than or equal to1.5 mg/dL
6. Serum ALT; greater than or equal to 31 and less than 200 U/L
9. The patients have to agree to join this study by their free wills after being well explained about this study.
10. Outpatient

Key exclusion criteria

The following patients should be excluded;
1. Infected with HBV or HCV
2. Alcohol assumption per day; greater than or equal to 30g for male, 20g/day for female
3. Accompanied with obvious malignant diseases including hepatoma
4. Accompanied with obvious hepatic encephalopathy
5. Accompanied with active infectious diseases (body temperature; higher or equal to 38 degree)
6.Accompanied with severe complications such as paralysis of intestine, ileus, interstitial pneumonia, pulmonary fibrosis, poorly controlled diabetes mellitus, heart failure, renal failure, liver failure, active ulcer and risky varix of digestive tract, and severe mental disturbance or depression etc.
7. Nursing woman and pregnant woman or the woman who may be pregnant
8. Taking contraindicating medicines with Febuxostat, such as mercaptopurine-hydrate, azathioprine, vidarabine, or didanosine.
9. Taking the following medicines which could affect serum uric acid within 4 weeks before considering entry of this study; losartan, fenofibrate, loop diuretic, or thiazide diuretic.
10. Taking the following uric acid-lowering medicines within 4 weeks before considering entry of this study; allopurinol, benzbromarone, probenecid, bucolome, or febuxostat.
11. Taking salicylated medicines everyday, however, the patients taking low dose of aspirin salicylate (less than or equal to 324 mg/day) cannot be excluded.
12.Taking estrogenic hormone everyday.
13. The other patients who the doctors in charge consider should not enter this study.

Target sample size

130

Name of lead principal investigator

1st name
Middle name
Last name	Tsuguhito Ota

Organization

Kanazawa University Hospital

Division name

Department of Diabetes, Metabolism, and Endocrinology

Zip code

Address

13-1, Takaramachi, Kanazawa, Ishikawa

TEL

076-265-2235

Email

shimakami@m-kanazawa.jp

Name of contact person

1st name
Middle name
Last name	Tetsuro Shimakami

Organization

Kanazawa University Hospital

Division name

Department of Gastroenterology

Zip code

Address

13-1, Takaramachi, Kanazawa, Ishikawa

TEL

076-265-2235

Homepage URL

Email

shimakami@m-kanazawa.jp

Institute

Kanazawa University Graduate School of Medical Science, Disease Control and Homeostasis

Institute

Department

Personal name

Organization

Teijin Pharma

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

5789

Org. issuing International ID_1

Kanazawa University Hospital, Center for Clinical Research Management

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

黒部市民病院（富山県）、富山労災病院（富山県）、厚生連滑川病院（富山県）、富山県立中央病院（富山県）、富山市民病院（富山県）、厚生連高岡病院（富山県）、市立砺波総合病院（富山県）、公立羽咋病院（石川県）、公立能登総合病院（石川県）、金沢医療センター（石川県）、金沢市立病院（石川県）、金沢赤十字病院（石川県）、石川県済生会金沢病院（石川県）、公立松任中央病院（石川県）、能美市立病院（石川県）、小松市民病院（石川県）、恵寿総合病院（石川県）、金沢有松病院（石川県）、やわたメディカルセンター（石川県）、河北中央病院（石川県）、加登病院（石川県）、北國クリニック（石川県）、福井県済生会病院（福井県）、くまがい内科クリニック（福井県）、市立敦賀病院（福井県）、

Date of disclosure of the study information

2012

Year

08

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

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

Recruitment status

Open public recruiting

Date of protocol fixation

2012

Year

07

Month

30

Day

Date of IRB

Anticipated trial start date

2012

Year

08

Month

15

Day

Last follow-up date

2014

Year

07

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

08

Month

14

Day

Last modified on

2014

Year

08

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010207