Glucocorticoid Therapy for COVID-19 Critically Ill Patients With Severe Acute Respiratory Failure

Study Overview
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Brief Summary
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In this multi-center, randomized, control study, the investigators will evaluate the efficacy and safety of glucocorticoid in combination with standard care for COVID-19 patents with Severe acute respiratory failure.

Detailed Description
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COVID-19 is a novel coronavirus that was initially outbreak in Wuhan, China. Severe acute respiratory infection with COVID-19 causes severe acute respiratory failure with substantial mortality. Currently, the standard care is supportive care, and no treatment is proven to be effective for this condition. Glucocorticoid therapy is widely used among critically ill patients with other coronavirus infection such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). However, whether glucocorticoid improved the outcome of COVID-19 remains unknown. We hypothesized that glucocorticoid would improve the prognosis of patietns with COVID-19. In this study, critically ill patients with COVID-19 were enrolled and randomized to receive ether standard care or standard care in combination with methylprednisolone therapy. The primary outcome is the difference of Murray lung injury score between two groups.

Official Title
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Glucocorticoid Therapy for Critically Ill Patients With Severe Acute Respiratory Infections Caused by COVID-19: a Prospective, Randomized Controlled Trial

Conditions
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COVID-19 Infections

Intervention / Treatment
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* Drug: methylprednisolone therapy
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult PCR confirmed COVID-19 infection Symptoms developed more than 7 days PaO2/FiO2 < 200 mmHg Positive pressure ventilation (non-invasive or invasive) or high flow nasal cannula (HFNC) higher than 45 L/min for less than 48 hours Requiring ICU admission Exclusion Criteria: pregnancy; patients currently taking corticosteroids (cumulative 400 mg prednisone or equivalent); Severe underlying disease, i.e. end stage of malignancy disease or end stage of pulmonary disease; Severe adverse events before ICU admission, i.e. cardiac arrest; Underlying disease requiring corticosteroids; Contraindication for corticosteroids; Recruited in other clinical intervention trial

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: standard care<br>standard care | Other: Standard care<br>* Standard care<br>|
| Experimental: standard care + methylprednisolone therapy<br>Methylprednisolone 40 mg q12h for 5 days | Drug: methylprednisolone therapy<br>* Methylprednisolone 40 mg q12h for 5 days<br>* Other names: Steroids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower Murray lung injury score | Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 4 according to the severity of the condition. | 7 days after randomization | 
| Lower Murray lung injury score | Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 4 according to the severity of the condition. | 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of PaO2/FiO2 between two groups | PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome. | 7 days after randomization | 
| Lower Sequential Organ Failure Assessment (SOFA) score | Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition. | 7 days after randomization | 
| Mechanical ventilation support | Percentage of patients requiring Mechanical ventilation support | 7 days after randomization | 
| The difference of PaO2/FiO2 between two groups | PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome. | 14 days after randomization | 
| Lower Sequential Organ Failure Assessment (SOFA) score | Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition. | 14 days after randomization | 
| Mechanical ventilation support | Percentage of patients requiring Mechanical ventilation support | 14 days after randomization | 
| Clearance of noval coronavirus | Clearance of noval coronavirus in upper respiratory tract or lower respiratory tract | 14 days after randomization | 
| All-cause mortality | All-cause mortality | 30 days after randomization |