Investigating the efficacy and tolerability of nintedanib therapy in idiopathic-inflammatory-myopathy-related interstitial lung disease

ISRCTN ISRCTN10507540
DOI https://doi.org/10.1186/ISRCTN10507540
Submission date
24/07/2020
Registration date
30/07/2020
Last edited
24/05/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Interstitial lung disease (ILD) is a group of lung conditions that affects the network of tissue (interstitium) that supports the air sacs of the lungs. ILD can cause stiffness in the lungs and lead to shortness of breath and death.

Idiopathic inflammatory myopathy (IIM) is a group of autoimmune disorders that cause inflammation of the muscles used for movement and lead to progressive muscle weakness. IIM can also affect non-muscular areas and the lung interstitium is the ILD is the most common non-muscular area affected. It is reported that 78% of IIM patients will develop ILD.

Idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD) is frequently aggressive and may not respond to conventional therapies including glucocorticoids and immunosuppressive drugs. Meanwhile, the rapid progression of interstitial lung disease (RP-ILD) is a major cause of death in IIM patients. It is therefore necessary to search for more successful treatment for IIM-ILD.

Nintedanib has been proven effective and relatively safe in idiopathic pulmonary fibrosis and systemic-sclerosis-associated interstitial lung disease, however, its efficacy and tolerability are not known in adult idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD). This study aims to assess how effective and well-tolerated nintedanib is in patients with IIM-ILD.

Who can participate?
Adult patients who regularly attend the outpatient or inpatient department of the study center with a diagnosis of IIM-ILD.

What does the study involve?
Patients who agree to participate will receive nintedanib therapy (150 mg, twice daily by mouth) in addition to standard treatment. Those who do not agree will receive standard immunosuppressive medication only.

What are the possible benefits and risks of participating?
Patients who received the nintedanib therapy may benefit from a therapeutic effect of nintedanib of slowing the progress of interstitial lung disease, reducing the chance of rapid progression, and improved survival. However, participants might experience side effects such as diarrhea and hepatic (liver) insufficiency as a result of this medication.

Where is the study run from?
The First Affiliated Hospital, College of Medicine, Zhejiang University (China)

When is the study starting and how long is it expected to run for?
From December 2017 to April 2020

Who is funding the study?
The National Natural Science Foundation of China (81701602) and Natural Science Foundation of Zhejiang Province (LQ20H100003) (China)

Who is the main contact?
Dr Junyu Liang
collinliangzju@zju.edu.cn

Contact information

Dr Junyu Liang
Public

79 Qingchun Road
Hangzhou
310003
China

ORCiD logoORCID ID 0000-0003-1050-1274
Phone +86 15168302715
Email collinliangzju@zju.edu.cn

Study information

Study designSingle-center interventional non-randomized real-world analysis pilot study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a participant information sheet
Scientific titleA real-world analysis of Nintedanib therapy in Idiopathic-inflammatory-myopathy-related Interstitial Lung Disease (NIILD): an efficacy and tolerability pilot study
Study acronymNIILD
Study objectivesNintedanib is efficient and relatively safe in adult idiopathic-inflammatory-myopathy-related interstitial lung disease.
Ethics approval(s)Approved 28/05/2020, the Research Ethics Committee of the First Affiliated Hospital of Zhejiang University (FAHZJU) (#79 Qingchun Road, Hangzhou, Zhejiang Province, P.R.China, 310003; +86 (0)571-87236629; zyiitlunli@163.com; kjkzyyy@163.com), ref: 2020-200, 2018-224
Health condition(s) or problem(s) studiedInterstitial lung disease in idiopathic inflammatory myopathy
InterventionParticipants who agree to participate will receive nintedanib (150 mg, twice daily, orally) in addition to traditional immunosuppressive therapy. Patients who do not agree to participate will only receive traditional immunosuprresive medications. The duration of treatment and follow-up should be at least 6 months.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Nintedanib
Primary outcome measure1. Occurrence of rapid progression of interstitial lung disease (RP-ILD), measured by the number of participants meeting the criteria of RP-ILD, assessed at the end of the follow-up. Patients with RP-ILD are defined as those presenting with progressive dyspnea and progressive hypoxemia, a worsening of interstitial change on the chest radiograph within 1 month after the initial visit or onset of respiratory symptoms.
Secondary outcome measures1. Time to death from any cause, measured through recording of survival or not and the length of follow-up, at the end of the follow-up. Cause of death will also be recorded in the follow-up such as exacerbation of interstitial lung disease, cardiopulmonary failure of unknown origin, pulmonary artery hypertension, etc.
2. Complications of pulmonary infection, measured and recorded in the process of follow-up, at the end of follow-up. Pulmonary infection will be identified based on International Statistical Classification of Diseases, 10th revision (ICD-10)-coded discharge diagnosis of community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), pulmonary fungal infection or pulmonary infection. Responsible pathogens were recognized based on repeated cultures/smears of bronchoalveolar lavage fluid (BALF) or sputum before related treatment.
3. Difference in immunosuppressive regimen such as dose of steroid, whether the potent and expensive intravenous immunoglobulin was used, etc. measured and recorded in the process of follow-up, at the end of follow-up
4. Tolerability of nintedanib will be measured as the incidence of adverse events, the incidence of dose reduction, or discontinuation due to adverse events, at the end of follow-up
Overall study start date01/12/2017
Completion date30/04/2020

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsover 100
Total final enrolment151
Key inclusion criteria1. Aged ≥18 years
2. Diagnosis of dermatomyositis, polymyositis or amyopathic dermatomyositis that meets the 2017 ACR/EULAR classification criteria
3. Attending a regular outpatient visit or hospitalization in the First Affiliated Hospital, College of Medicine, Zhejiang University
Key exclusion criteria1. Overlap syndromes with other connective tissue diseases (CTDs)
2. Attending outpatient visit or hospitalization for reasons unrelated to myositis and its complications, such as fracture, pregnancy, acquired immunodeficiency syndrome, cataract, and etc.
3. Previous use of nintedanib, or previous/present use of pirfenidone
4. Loss to follow-up without death from any cause within 6 months after the initial outpatient visit or hospitalization
Date of first enrolment01/01/2018
Date of final enrolment31/10/2019

Locations

Countries of recruitment

  • China

Study participating centre

First Affiliated Hospital Zhejiang University
Department of Rheumatology
79 Qingchun Road
Hangzhou
310003
China

Sponsor information

National Natural Science Foundation of China
Government

83 Shuangqing Road
Haidian District
Beijing
100085
China

Phone +86 (0)10-62328991
Email yxzhc-1@nsfc.gov.cn
Website http://www.nsfc.gov.cn/
ROR logo "ROR" https://ror.org/01h0zpd94
Natural Science Foundation of Zhejiang Province
Government

Provincial Natural Science Foundation Office
3rd floor
Computing Institute
Building 4
Provincial Government
33 Huancheng West Road
Hangzhou City
Hangzhou
310006
China

Phone +86 (0)571-88212780
Email cy@zjnsf.gov.cn
Website http://www.zjnsf.gov.cn/
ROR logo "ROR" https://ror.org/05m1p5x56

Funders

Funder type

Government

National Natural Science Foundation of China
Government organisation / National government
Alternative name(s)
Chinese National Science Foundation, Natural Science Foundation of China, National Science Foundation of China, NNSF of China, NSF of China, 国家自然科学基金委员会, National Nature Science Foundation of China, Guójiā Zìrán Kēxué Jījīn Wěiyuánhuì, NSFC, NNSF, NNSFC
Location
China
Natural Science Foundation of Zhejiang Province
Government organisation / Local government
Alternative name(s)
Zhejiang Natural Science Foundation, 浙江省自然科学基金根据国, 浙江省自然科学基金根据国, Zhejiang Provincial Natural Science Foundation, Zhejiang Provincial Natural Science Fund, ZJNSF
Location
China

Results and Publications

Intention to publish date01/10/2020
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal.
IPD sharing planData including therapy duration, doses, adverse events, age, and sex of patients receiving nintedanib therapy will be available as supplements of the future publication. Other parts of the data in this study will be provided upon request.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 03/02/2021 24/05/2021 Yes No

Editorial Notes

24/05/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
29/07/2020: Trial’s existence confirmed by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang University.