UMIN-CTR Clinical Trial

Public title

Evaluation of the clinical remission and its sustainment after discontinuation of infliximab in patients with rheumatoid arthritis who receive "programmed" treatment in randomized controlled trial

Acronym

Remission induction by Raising the dose of Remicade in RA study (RRRR Study)

Scientific Title

Evaluation of the clinical remission and its sustainment after discontinuation of infliximab in patients with rheumatoid arthritis who receive "programmed" treatment in randomized controlled trial

Scientific Title:Acronym

Remission induction by Raising the dose of Remicade in RA study (RRRR Study)

Region

Japan

Condition

Rheumatoid Arthritis

Classification by specialty

Endocrinology and Metabolism

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the frequency of clinical remission and its sustainment after discontinuation of infliximab (IFX) in methotrexate-refractory patients with rheumatoid arthritis who receive "programmed" treatment (programmed treatment arm), whose dose of IFX for each patient is determined by the baseline tumor necrosis factor-alpha (TNF-alpha) level, compared with patients who receive a "standard" treatment (standard treatment arm), whose dose was fixed as 3mg/kg every 8 weeks, as a control in a prospective randomized controlled trial.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Proportion of patients maintaining discontinuation of IFX at 1 year after a discontinuation of IFX at the time of 54 weeks after the first administration of IFX

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

"programmed" treatment (Programmed treatment arm), whose dose of IFX for each patient is determined by the baseline TNF-alpha level
IFX 3mg/kg is administered on week 0, 2 and 6. After week 14, dose of IFX for each patient is determined by the baseline TNF-alpha level as follows;
TNF-alpha < 0.55pg/mL: IFX 3mg/kg is continued every 8 weeks.
0.55pg/mL =< TNF-alpha < 1.65pg/mL: IFX 6mg/kg is administered on week 14. IFX 6mg/kg is continued every 8 weeks.
TNF-alpha >= 1.65pg/mL: IFX 6mg/kg is administered on week 14 and IFX 10mg/kg is administered on week 22. IFX 10mg/kg is continued every 8 weeks.
In all cases, IFX is discontinued at the time of 54 weeks after the first administration of IFX.

Interventions/Control_2

"standard" treatment (standard treatment arm), whose dose was fixed as 3mg/kg every 8 weeks
IFX 3mg/kg is administered on week 0, 2 and 6. After week 14, IFX 3mg/kg is continued every 8 weeks. IFX is discontinued at the time of 54 weeks after the first administration of IFX.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) rheumatoid arthritis, 2) refractory patients despite methotrexate, 3) patients who have never treated with IFX, 4) written informed consent

Key exclusion criteria

1) patients who use steroid over 10mg/day (prednisolone-equivalent), 2) SDAI =< 11.0, 3) severe infection, 4) active tuberculosis, 5) demyelinating disease, 6) congestive heart failure, 7) Patient who is lactating, pregnant, possibly pregnant or do not agree with anti-conception during the trial and 6 month after the last administration of IFX, 8) patients who are inadequate to enter this trial due to the other reasons by physician's judgments

Target sample size

450

Name of lead principal investigator

1st name
Middle name
Last name	Yoshiya Tanaka

Organization

University of Occupational and Environmental Health, Japan

Division name

The First Department of Internal Medicine, School of Medicine

Zip code

Address

1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Japan

TEL

093-603-1611

Email

tanaka@med.uoeh-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Nao Horie

Organization

Hokkaido University Hospital

Division name

Translational Research and Clinical Trial Center

Zip code

Address

Nishi-5, Kita-14, Kita-ku, Sapporo, Hokkaido, Japan

TEL

011-706-7735

Homepage URL

Email

nhorie@med.hokudai.ac.jp

Institute

University of Occupational and Environmental Health, Japan

Institute

Department

Personal name

Organization

a Research Grant-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan (partly), Self funding

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

産業医科大学（福岡県）・早石会早石病院（大阪府）・東京医科歯科大学（東京都）・千葉大学医学部付属病院（千葉県）・長崎大学病院（長崎県）・東北大学病院（宮城県）・埼玉医科大学病院総合医療センター（埼玉県）・青梅市総合病院（東京都）・善仁会市民の森病院（宮崎県）・市立札幌病院（北海道）・北海道内科リウマチ科病院（北海道）・埼玉医科大学（埼玉県）・弘前大学医学部付属病院（青森県）・天理よろづ相談所病院（奈良県）・島根大学医学部付属病院（島根県）・東京大学医学部付属病院（東京都）・横浜市立みなと赤十字病院（神奈川県）・川崎市立川崎病院（神奈川県）・青森県立中央病院（青森県）・名古屋大学医学部（愛知県）・牛尾整形外科（大阪府）・北海道大学病院（北海道）・本荘リウマチクリニック（富山県）・久留米大学医療センター（福岡県）・筑波大学附属病院（茨城県）・順天堂大学（東京都）・愛知医科大学病院（愛知県）・鹿児島赤十字病院（鹿児島県）・慶應義塾大学（東京都）・山形大学医学部附属病院（山形県）・昭和大学病院（東京都）・横浜南共済病院（神奈川県）・京都大学医学部附属病院（京都府）・松原メイフラワー病院（兵庫県）・宇多野病院（京都府）・京都下鴨病院（京都府）・市立長浜病院（滋賀県）・大阪赤十字病院（大阪府）・日本赤十字社和歌山医療センター（和歌山県）・佐世保中央病院（長崎県）・兵庫医科大学（兵庫県）・宇多津浜クリニック（香川県）・名古屋市立大学病院（愛知県）・北里大学病院（神奈川県）・藤田保健衛生大学（愛知県）・・高知大学　医学部（高知県）・関西医科大学付属枚方病院（大阪府）・国立病院機構千葉東病院（千葉県）・岡山大学病院（岡山県）・広島大学病院（広島県）

Date of disclosure of the study information

2011

Year

03

Month

31

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

Completed

Date of protocol fixation

2011

Year

02

Month

17

Day

Date of IRB

2011

Year

03

Month

07

Day

Anticipated trial start date

2011

Year

04

Month

01

Day

Last follow-up date

2016

Year

10

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2019

Year

03

Month

31

Day

Other related information

Registered date

2011

Year

02

Month

21

Day

Last modified on

2019

Year

03

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006076