Acute Respiratory Distress Syndrome
Conditions
Keywords
Acute Respiratory Distress Syndrome, Corticosteroid, Glucocorticoid
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.
Interventions
DRUGIntravenous glucocorticoid therapy
Betamethasone, dexamethasone, or methylprednisolone
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Moderate to severe ARDS with a P/F ratio \< 200 mmHg 2. On invasive mechanical ventilation 3. The onset of ARDS \< 72 hours
Exclusion criteria
1. Age \<20 years 2. Receiving systemic glucocorticoid therapy 3. Uncontrolled gastrointestinal bleeding 4. Terminal cancer 5. Post-operation or with large wound 6. Considered by the primary care doctor to be either definitely indicated or definitely contraindicated for glucocorticoid therapy 7. Anticipating to receive chemotherapy and immunotherapy in 3 months 8. Uncontrolled fungal infection 9. Post solid organ or bone marrow transplant 10. Severe influenza without anti-viral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free survival | 28 days | Ventilator-free survival between control and intervention arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucocorticoid treatment duration and ventilator-free survival | 28 days | Ventilator-free survival between long treatment duration and short treatment duration groups |
| ICU mortality | Length of ICU stay up to 28 days | Between-group difference in mortality at ICU discharge |
| Hospital mortality | Length of hospital stay up to 60 days | Between-group difference in mortality at hospital discharge |
| 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 |
| Glucocorticoid dose and ventilator-free survival | 28 days | Ventilator-free survival between low-dose and moderate-dose glucocorticoid groups |
| Successful liberation from mechanical ventilation | Up to 60 days | Median time to successful liberation from mechanical ventilation |
| Lymphocytopenia | 7 days | Proportion of lymphocytopenia on day 7 |
| Blood glucose level | 10 days | Peak blood glucose level during treatment |
| Hyperglycemia | 10 days | Proportion of patients with hyperglycemia during treatment |
| Rapid oxygenation improvement | 3 days | Change in P/F ratios between day 1 and day 3 |
Outcome results
None listed