UMIN-CTR Clinical Trial

Basic information
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
Condition	Interstitial lung disease related to rheumatoid arthritis
Classification by specialty	Clinical immunology
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
Last 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

Public contact
1st 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

Sponsor
Institute	Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University
Institute
Department

Funding Source
Organization	Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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	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

Other administrative information
Date of disclosure of the study information	2013 Year 02 Month 26 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
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
Other related information

Management information
Registered date	2013 Year 02 Month 26 Day
Last modified on	2019 Year 03 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000011860