Glucocorticoid Therapy for Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Acute respiratory distress syndrome (ARDS) is a clinical syndrome of inflammatory lung injury characterized by increased pulmonary vascular permeability, loss of aerated lung tissue, severe hypoxemia and impaired compliance. Despite the advance in the critical care technology, the mortality of ARDS remains high in the last decades. Glucocorticoids have profound anti-inflammatory actions through the pleiotropic effects of the glucocorticoid receptor, which are considering a promising pharmacological therapy to mitigate the inflammatory lung injury and subsequent fibrosis in ARDS. Previous clinical trials have repeatedly tested the efficacy of glucocorticoid therapy in ARDS; however, the data about hard outcomes, such as mortality, are inconsistent between these studies. Investigators designed a 3x2 factorial trial of glucocorticoid therapy in ARDS to test the effects of glucocorticoid dosages (dose 0, dose 0.5 mg/kg, and dose 1 mg/kg of methylprednisolone equivalence) and durations (prolonged and short duration) on the treatment efficacy. In addition, investigators will measure the change of inflammatory biomarkers for post-hoc analysis to explore whether biomarkers could be used to guide patient selection and steroid tapering.

Official Title
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A Factorial Trial of Glucocorticoid Therapy in Acute Respiratory Distress Syndrome: Optimizing Dosing Regimen and Developing Biomarker-guided Treatment

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Intravenous glucocorticoid therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe ARDS with a P/F ratio < 200 mmHg On invasive mechanical ventilation The onset of ARDS < 72 hours Exclusion Criteria: Age <20 years Receiving systemic glucocorticoid therapy Uncontrolled gastrointestinal bleeding Terminal cancer Post-operation or with large wound Considered by the primary care doctor to be either definitely indicated or definitely contraindicated for glucocorticoid therapy Anticipating to receive chemotherapy and immunotherapy in 3 months Uncontrolled fungal infection Post solid organ or bone marrow transplant Severe influenza without anti-viral therapy

Ages Eligible for Study
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Minimum Age: 20 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Standard care without glucocorticoid therapy. | |
| Experimental: Low dose and long treatment duration<br>Methylprednisolone equivalent dose 0.5 mg/kg/day for 5 days, followed by 0.25 mg/kg/day for 5 days. | Drug: Intravenous glucocorticoid therapy<br>* Betamethasone, dexamethasone, or methylprednisolone<br>|
| Experimental: Low dose and short treatment duration<br>Methylprednisolone equivalent dose 0.5 mg/kg/day for 4 days,, followed by 0.25 mg/kg/day for 3 days. | Drug: Intravenous glucocorticoid therapy<br>* Betamethasone, dexamethasone, or methylprednisolone<br>|
| Experimental: Moderate dose and long treatment duration<br>Methylprednisolone equivalent dose 1 mg/kg/day for 5 days, followed by 0.5 mg/kg/day for 5 days. | Drug: Intravenous glucocorticoid therapy<br>* Betamethasone, dexamethasone, or methylprednisolone<br>|
| Experimental: Moderate dose and short treatment duration<br>Methylprednisolone equivalent dose 1 mg/kg/day for 4 days, followed by 0.5 mg/kg/day for 3 days. | Drug: Intravenous glucocorticoid therapy<br>* Betamethasone, dexamethasone, or methylprednisolone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free survival | Ventilator-free survival between control and intervention arms | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucocorticoid dose and ventilator-free survival | Ventilator-free survival between low-dose and moderate-dose glucocorticoid groups | 28 days | 
| Glucocorticoid treatment duration and ventilator-free survival | Ventilator-free survival between long treatment duration and short treatment duration groups | 28 days | 
| ICU mortality | Between-group difference in mortality at ICU discharge | Length of ICU stay up to 28 days | 
| Hospital mortality | Between-group difference in mortality at hospital discharge | Length of hospital stay up to 60 days | 
| 60-day mortality | Between-group difference in mortality by day 60 | 60 days | 
| Oxygenation on day 7 | Proportion of patients with a P/F ratio > 200 mmHg on day 7 | 7 days | 
| Rapid oxygenation improvement | Change in P/F ratios between day 1 and day 3 | 3 days | 
| Successful liberation from mechanical ventilation | Median time to successful liberation from mechanical ventilation | Up to 60 days | 
| Lymphocytopenia | Proportion of lymphocytopenia on day 7 | 7 days | 
| Blood glucose level | Peak blood glucose level during treatment | 10 days | 
| Hyperglycemia | Proportion of patients with hyperglycemia during treatment | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Corticosteroid, Glucocorticoid