UMIN-CTR Clinical Trial

Public title

A parallel group, randomized clinical trial on the efficacy and safety of intensive treatment strategy with MTX as the anchor-drug in patients with active early rheumatoid Arthritis

Acronym

An intensive treatment strategy in patients with active early RA

Scientific Title

A parallel group, randomized clinical trial on the efficacy and safety of intensive treatment strategy with MTX as the anchor-drug in patients with active early rheumatoid Arthritis

Scientific Title:Acronym

An intensive treatment strategy in patients with active early RA

Region

Japan

Condition

rheumatoid arthritis

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

In this study, we have co-primary endpoints. First, we compare the efficacy and safety between the intensive treatment strategy aiming at achieving and maintaining remission and the conventional treatment strategy in Japanese patients with active early RA. Second, we identify factors that contribute to achieving clinical remission and improvement of physical function. Secondary endpoint is to provide data and evidence when reviewing Japanese guideline for RA in future.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Remission rates at week 24 by SDAI or Boolean index

Key secondary outcomes

1.Remission rates at week 48 and 72 by SDAI and Boolean index
2.Achievement rates for low disease activity status by SDAI and CDAI at weeks 24, 48 and 72
3.Changes of ACR20,50,70 over time
4.Changes of ACR-hybrid, SDAI, CDAI, and DAS28 over time
5.Changes of sigmaSDAI, sigmaCDAI, sigmaDAS28, vdH-modified TSS score, JSN score and erosion score from baseline and achievement rate of structural remission at weeks 24, 48 and72
6.Changes of physical function (EQ-5D, full HAQ) over time and functional remission rates at weeks 24, 48 and 72
7.Safety (incidence and types of adverse events, severe adverse events, adverse drug reactions, and serious adverse drug reactions)
8.Identification of prognostic factor for clinical remission, functional remission, and normalization of physical function

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Intensive treatment group
Period: 24 weeks
In the intensive treatment group, a patient starts treatment with MTX at 8mg/week. Dosage is increased to 0.25mg/kg/week by week 8 and is further increased to his or her maximum tolerable dosage by week 12. The maximum tolerable dosage is maintained until week 24. If a patient shows inadequate response to MTX and does not achieve SDAI(simplified disease activity index)emission or CDAI (linical disease activity index)remission by week 16, additional treatment with tacrolimus, bucillamine, sarazosulfapyridine, or biologics will be started as scheduled in the protocol.
After week 24, both groups receive treatments by attending rheumatologists'discretion and are followed until week 72.

Interventions/Control_2

Conventional treatment group
Period: 24 weeks
In the control group, a patient starts treatment with MTX, tacrolimus, bucillamine, sarazosulfapyridine, or biologics by attending rheumatologists' discretion by week 24. Biologics are allowed on and after week 12. After week 24, both groups receive treatments by attending rheumatologists'discretion and are followed until week 72.

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

70

years-old

>=

Gender

Male and Female

Key inclusion criteria

A Patient of rheumatoid arthritis (RA) who meets all of the following will be eligible to the study.
1.A patient who develops arthritis within 2 years before the enrollment and who fulfills the 2010 ACR/EULAR classification criteria for RA
2.A patient who has SDAI>11
3.A patient who is 20 to 70 years old and gives written informed consent
4.A patient who has never received MTX, tacrolimus, and biologics.
5.A patient who can use MTX
6.A patient who has not started any DMARDs within the last 4weeks.
7.A patient who has not received intravenous or intra-articular injection of corticosteroid within the last 4weeks.
8.A patient who has equal or more than 4 swollen joints and equal or more than 4 tender joints (using 66- or 68-joint count, respectively)
9.Patients who meets any of the following criteria 1) positive serology (rheumatoid factor or anti-CCP antibody), 2) typical bone erosion for RA by X-ray, 3) CRP equal or more than 0.8mg/dL

Key exclusion criteria

A patient who has any of the following will be excluded from the study.
1.When a patient refuses to give or withdraws his or her consent.
2.A patient who with concurrent other inflammatory joint diseases (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, SLE, systemic sclerosis and mixed connective tissue disease), or history of these diseases. Sjogren syndrome is not included in these diseases.
3.When a patient has contraindications for MTX or tacrolimus.
4.When a patient has an active infectious disease.
5.A patient who is positive for HBs antigen or HBV DNA is excluded unless he/she receive nucleotide analogue and becomes negative for HBV DNA.
6.When a patient has severe hepatic disease, which is contraindication for MTX.
7.When a patient has severe renal disease, which is contraindication for MTX
8.When a patient has concurrent malignancy, lymphoma, leukemia or lymphproliferative disorder except for skin cancer (basal cell carcinoma or epithelial cell carcinoma) and cervical cancer of uterus which were completely resected and has not recurred for more than 5 years,
9.When a patient has uncontrollable comorbidities (i.e., severe diabetes, unstable ischemic heart disease, stroke within the last 1 year).
10.A patient with latent tuberculosis unless he/she receives proper chemoprophylaxis according to the Japan College of Rheumatology guideline.
11.When a patient received investigational drug within the last month or within the five times of half-life, whichever is longer.
12.When a patient's body weight less than 40kg.
13.When a patient is under breastfeeding or pregnant, or has plan to be pregnant in 24 weeks.
14.When a doctor judges a patient cannot to visit outpatient clinic regularly for 24 weeks.
15.When a doctor judges a patient not appropriate to participate in the study.

Target sample size

290

Name of lead principal investigator

1st name
Middle name
Last name	Masayoshi Harigai

Organization

Tokyo Medical and Dental University

Division name

Department of Pharmacovigilance, Department of Medicine and Rheumatology

Zip code

Address

1-5-45,Yushima 1-chome, Bunkyo-ku, Tokyo

TEL

03-5803-4677

Email

mharigai.mpha@tmd.ac.jp

Name of contact person

1st name
Middle name
Last name	Michi Tanaka

Organization

Tokyo Medical and Dental University

Division name

Department of Pharmacovigilance

Zip code

Address

1-5-45,Yushima 1-chome, Bunkyo-ku, Tokyo

TEL

03-5803-4677

Homepage URL

Email

tanaka.phv@tmd.ac.jp

Institute

Tokyo Medical and Dental University

Institute

Department

Personal name

Organization

ministry of health, labour, and welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Co-sponsor

Department of Pharmacovigilance

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

東京医科歯科大学・埼玉医科大学総合医療センター・慶應義塾大学・長崎大学・国立病院機構相模原病院・北海道大学・新潟県立リウマチセンター・宇多津浜クリニック・横浜市立大学・東広島記念病院・日立製作所多賀総合病院・道後温泉病院・草加市立病院・産業医科大学・東京都健康長寿医療センター・順天堂大学・香川大学・青梅市立総合病院・国家公務員東京共済病院・横浜市立みなと赤十字病院・筑波大学・宮崎市民の森病院・熊本大学・京都大学
Tokyo medical and dental university, Saitama medical center, Keio university, Nagasaki university, NHO Sagamihara national hospital, Hokkaido university, Niigata rheumatic center, Utazuhama clinic, Yokohama city university, Higashi hiroshima memorial hospital, Taga general hospital, Dohgo spa hospital, Soka municipal hospital, University of occupational and environmental health, Tokyo metropolitan geriatric hospital, Juntendo university, Kagawa university, Ome municipal general hospital, Tokyo kyosai Hospital, Yokohama city minato red cross hospital, Tsukuba university, Shiminnomori hospital, Kumamoto university, Kyoto university.

Date of disclosure of the study information

2011

Year

11

Month

11

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

No longer recruiting

Date of protocol fixation

2011

Year

09

Month

05

Day

Date of IRB

Anticipated trial start date

2012

Year

02

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

11

Month

11

Day

Last modified on

2014

Year

05

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007922