The Efficacy and Safety of Tocilizumab for Severe RP-ILD Secondary to Systemic Diseases

Study Overview
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Brief Summary
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There is no confirmed drug therapy for RP-ILD. Prognosis is poor of regular treatment. The study is designed to compare efficacy and safety of tocilizumab versus regular treatment in participants with severe RP-ILD secondary to systemic diseases.

Detailed Description
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RP-ILD, also known as the acute exacerbation of interstitial lung disease, was defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality on chest imaging or histopathology. It is rapidly progressive and life-threatening. Despite aggressive regular treatments with high-dose glucocorticoids in combination with immunosuppressant drugs such as cyclosporine, tacrolimus, or cyclophosphamide, the post-exacerbation mortality rates remain high. There is no confirmed drug therapy for RP-ILD. Recently, the exacerbation of interstitial lung diseases secondary to systemic diseases was proved to involve many inflammatory responses, so patients are more likely to benefit from immune regulation therapy. Tocilizumab is a monoclonal antibody that inhibits the binding of interleukin-6 (IL-6), a multifunctional cytokine that regulates the immune response and inflammation, to its receptor (IL-6R). The study is designed to compare efficacy and safety of tocilizumab versus regular treatment in participants with severe RP-ILD secondary to systemic diseases.

Official Title
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A Prospective, Randomized Controlled Study to Compare Efficacy and Safety of Intravenous 8mg/kg Tocilizumab Versus Regular Treatment for Severe Rapid Progressive Interstitial Lung Diseases (RP-ILD) Secondary to Systemic Diseases

Conditions
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Rapid Progressive Interstitial Lung Diseases

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RP-ILD, previous or concurrent diagnosis of systemic diseases Exclusion Criteria: pregnancy; uncontrolled pulmonary infections; severe cardiovascular, hepatic and renal dysfunction; unstable angina or myocardial infarction; thrombocytopenia； neutrophil reduction； malignant tumor; allergy to tocilizumab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are planned to be separated into two groups. 68 participants with severe RP-ILD secondary to systemic diseases will be randomly assigned to receive intravenous 8mg/kg tocilizumab or regular treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab<br>Participants in tocilizumab group will receive intravenous 8mg/kg tocilizumab. No Intervention: control, participants in control group will receive regular treatment. | Drug: Tocilizumab<br>* Participants in tocilizumab group will receive intravenous 8mg/kg tocilizumab.<br>|
| No Intervention: Control<br>Participants in control group will receive regular treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The differences of oxygenation index changes between the two groups on day 7, 14, 28 and month 3 after the first dose* | first dose: The tocilizumab group: the tocilizumab administered for the first time; The control group: the maximum dose of glucocorticoid administered for the first time | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical stability | clinical stability was defined as on the first day that all of the following criteria are simultaneously achieved: (1) Participants can tolerate walking with or without oxygen therapy; (2) no wheeze; and (3) oxygen saturation >88% on room air. | 3 months | 
| Survival rate after 3 months |  | 3 months | 
| Length of stay in hospital |  | 3 months | 
| Length of stay in ICU |  | 3 months | 
| Changes of dyspnea index |  | 3 months | 
| The occurrence of adverse events within 1, 3, 7, 14, 28 days and 3 months after the first dose | adverse events: sepsis, treatment-related hyperglycemia, gastrointestinal bleeding, hospital infection | 3 months | 
| Changes of erythrocyte sedimentation rate, c-reactive protein or ferritin at baseline and on day 3, 7, 14, 28, month 3 after the first dose |  | 3 months | 
| Computed tomography score |  | 3 months | 
| Hospitalization cost |  | 3 months | 
| Re-admission rate |  | 3 months |