Glucocorticoid Therapy for Acute Respiratory Distress Syndrome

Phase 2

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Low dose and long treatment duration	Intravenous glucocorticoid therapy	Methylprednisolone equivalent dose 0.5 mg/kg/day for 5 days, followed by 0.25 mg/kg/day for 5 days.
Moderate dose and long treatment duration	Intravenous glucocorticoid therapy	Methylprednisolone equivalent dose 1 mg/kg/day for 5 days, followed by 0.5 mg/kg/day for 5 days.
Moderate dose and short treatment duration	Intravenous glucocorticoid therapy	Methylprednisolone equivalent dose 1 mg/kg/day for 4 days, followed by 0.5 mg/kg/day for 3 days.
Low dose and short treatment duration	Intravenous glucocorticoid therapy	Methylprednisolone equivalent dose 0.5 mg/kg/day for 4 days,, followed by 0.25 mg/kg/day for 3 days.

Primary Outcome Measures

Name	Time	Method
Ventilator-free survival	28 days	Ventilator-free survival between control and intervention arms

Secondary Outcome Measures

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