UMIN-CTR Clinical Trial

Public title

Efficacy and safety of treatment with moderate doses of corticosteroid and immunosuppressants in rheumatoid arthritis patients with interstitial lung disease

Acronym

Efficacy and safety of treatment with moderate doses of corticosteroid and immunosuppressants in RA-ILD

Scientific Title

Efficacy and safety of treatment with moderate doses of corticosteroid and immunosuppressants in rheumatoid arthritis patients with interstitial lung disease

Scientific Title:Acronym

Efficacy and safety of treatment with moderate doses of corticosteroid and immunosuppressants in RA-ILD

Region

Japan

Condition

Interstitial lung disease related to rheumatoid arthritis

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study is to evaluate efficacy and safety of treatment with moderate doses of corticosteroid and immunosuppressants in newly developed or recurrent cases of interstitial lung disease (categorized into either UIP, NSIP or OP pattern based on HRCT findings) related to rheumatoid arthritis

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

For cases with UIP/NSIP pattern ILD, improvement in forced vital capacity (FVC), which is defined as 10% or 200ml increase in FVC at week 24
For cases with OP pattern ILD, improvement of HRCT findings which is defined as 1 or more score improvement of Kazerooni score in affected lobes at week 24

Key secondary outcomes

Symptoms related to interstitial lung disease (Borg scale, MRC dyspnoea scale, UCSD shortness of breath questionnaire), improvement of HRCT findings (Kazerooni score), pulmonary function tests (change in FVC, diffusing capacity of the lung for CO), change in a serum marker (KL-6), a relapse rate of interstitial lung disease requiring increase in the dose of corticosteroid, activity of rheumatoid arthritis(SDAI, CDAI), adverse events, infectious events

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

In cases with UIP/NSIP pattern ILD, treatment is started with prednisolone and tacrolimus. For safety concern, the doses of tacrolimus should not exceed the dose approved in Japan and are adjusted to maintain blood trough levels less than 10 ng/ml. Prednisolone is started at the dose of 0.5 mg/kg/day and continued at the initial dose through 2-4 weeks, then reduced by 5 mg every 2-4 weeks. After the dose of prednisolone reaches 15 mg/day, it is reduced by 2.5 mg. After the dose of prednisolone reaches 10 mg, it is reduced by 1 mg every 4 weeks. The dose of prednisolone should be tapered to achieve 0.2 mg/kg/day at week 24. Prednisolone should be maintained at least 5 mg/day until month 12. Then prednisolone can be either continued, reduced or stopped later on.
In cases with OP pattern ILD, prednisolone is started, tapered and maintained as mentioned in cases with UIP/NSIP pattern ILD. Methotrexate is started after the dose of prednisolone reaches 0.3 to 0.4 mg/kg/day. Methotrexate is increased to the maximal tolerable dose, but should not exceed 16 mg/week. Methotrexate should be used following the guideline published by Japan College of Rheumatology. If methotrexate is not feasible by any reason, it can be substituted by tacrolimus and tacrolimus should be used as mentioned in UIP/NSIP pattern ILD cases.

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

Patients must meet the following criteria to be eligible for this study.
1. Fulfill the 2010 ACR/EULAR classification criteria for RA
2. Aged 20 years or older
3. Have newly developed or recurrent RA-related ILD, which is categorized as either UIP, NSIP or OP pattern based on HRCT findings. A patient who meets either of the following conditions.

1)A patient with newly developed RA-related ILD which is categorized as either UIP or NSIP pattern based on HRCT findings
2)A patient with recurrent ILD (a patient must fulfill both i. and ii.)
i. A patient has a history of RA-related ILD which was categorized as either UIP or NSIP pattern based on previous image findings (HRCT is preferable)
ii. A patient has exacerbation of ILD or ILD is considered to be active based on HRCT findings.
3)A patient with newly developed RA-related ILD which is categorized as an OP pattern based on HRCT findings.
4)A patient with recurrent RA-related ILD which is categorized as an OP pattern based on HRCT findings.

Key exclusion criteria

A patient who has any of the following conditions will be excluded from this study.
1. When a patient has acute exacerbation of interstitial lung disease (when a patient has acutely progressive bilateral lung infiltration and is considered to be inappropriate for the study entry by the attending physician)
2. When a patient has pulmonary hemorrhage
3. When a patient is considered to require positive pressure ventilation (positive pressure ventilation via endotracheal intubation or noninvasive positive pressure ventilation)
4. When a patient is diagnosed as having active respiratory infection or drug-induced pneumonia
5. In a case with ILD of UIP or NSIP pattern, when tacrolimus is contraindicated or a patient has ever treated with tacrolimus for ILD before
6. In a case with ILD of OP pattern, both MTX and tacrolimus are contraindicated or a patient has ever treated by either MTX or tacrolimus for ILD
7. When a patient is considered to require prednisolone with the dose of more than 0.5 mg/kg/day
8. When a patient has moderate or severe pulmonary hypertension or heart failure
9. When a patient has collagen vascular disease other than rheumatoid arthritis (Sjogren's syndrome is permissible)
10. When a patient has severe organ involvement other than interstitial lung disease
11. When a patient is considered as ineligible for this study for any reason by the attending physician

Target sample size

34

Name of lead principal investigator

1st name
Middle name
Last name	Masaaki Mori

Organization

Tokyo Medical and Dental University

Division name

Department of Lifetime Clinical Immunology

Zip code

Address

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

TEL

03-5803-4677

Email

masaaki.mori.mm@gmail.com

Name of contact person

1st name
Middle name
Last name	Fumio Hirano

Organization

Tokyo Medical and Dental University

Division name

Department of Lifetime Clinical Immunology

Zip code

Address

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

TEL

03-5803-4677

Homepage URL

Email

hirano.rheu@tmd.ac.jp

Institute

Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University

Institute

Department

Personal name

Organization

Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

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

東京医科歯科大学(東京都)、青梅市立総合病院(東京都)、東京都健康長寿医療センター(東京都)、横浜市立みなと赤十字病院(神奈川県)、国家公務員東京共済病院(東京都)、草加市立病院(埼玉県)、武蔵野赤十字病院(東京都)
Tokyo Medical and Dental University, Ome Municipal General Hospital, Tokyo Metropolitan Geriatric Hospital, Yokohama City Minato Red Cross Hospital, Tokyo Kyosai Hospital, Soka Municipal Hospital, Japanese Red Cross Musashino Hospital

Date of disclosure of the study information

2013

Year

02

Month

26

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

2013

Year

02

Month

25

Day

Date of IRB

2013

Year

02

Month

25

Day

Anticipated trial start date

2013

Year

02

Month

25

Day

Last follow-up date

2019

Year

03

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

02

Month

26

Day

Last modified on

2019

Year

03

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011860