Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19
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Design
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Ongoing, international, multicenter, open-label trial
N=403
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Objective
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To determine whether hydrocortisone improves outcomes for patients with severe Coronavirus Disease (COVID)-19
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Study Groups
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Fixed-dose hydrocortisone (n= 143)
Shock-dependent hydrocortisone (n= 152)
No hydrocortisone (n= 108)
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Inclusion Criteria
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Adults with presumed or confirmed COVID-19 infection who were admitted to an intensice care unit (ICU) for respiratory or cardiovascular organ support
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Exclusion Criteria
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Presumption of imminent death, systemic corticosteroid use, more than 36 hours elapsed since ICU admission
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Methods
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Patients were randomized to receive a fixed dose of intravenous hydrocortisone, 50 mg every six hours for seven days; intravenous hydrocortisone, 50 mg every 6 hours while in shock for up to 28 days; or no hydrocortisone. Hydrocortisone was discontinued in the shock-dependent group once shock was considered to have resolved or vasopressors had been discontinued for 24 hours.
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Duration
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Up to 21 days
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Outcome Measures
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Primary outcome: respiratory and cardiovascular organ support–free days up to day 21
Secondary outcomes: Hospital mortality, Median organ support-free days among survivors
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Baseline Characteristics
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Fixed-dose hydrocortisone (n= 137)
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Shock-dependent hydrocortisone (n= 146)
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No hydrocortisone (n= 101)
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Age, years
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60.4 ± 11.6
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59.5 ± 12.7
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59.9 ± 14.6
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Men
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98 (71.5%)
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103 (70.6%)
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72 (71.3%)
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Confirmed SARS-CoV-2 Infection
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109/134 (81.3%)
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87/125 (69.6%)
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79/100 (79.0%)
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Time to Enrollment (IQR)
From hospital admission, days
From ICU admission, hours
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1.2 (0.8-2.6)
15.1 (7.5-19.8)
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1.0 (0.7-2.8)
12.3(5.4-18.8)
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1.1 (0.7-2.0)
13.5 (8.1-17.5)
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Acute Respiratory Support
None
High-flow nasal cannula
Noninvasive MV
Invasive MV
ECMO
Vasopressor support
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0
17 (12.4%)
33 (24.1%)
87 (63.5%)
1/137 (0.7%)
56 (40.9%)
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1 (0.7%)
23 (15.8%)
49 (33.6%)
73 (50.0%)
0/143
47 (32.2%)
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0
16 (15.8%)
32 (31.7%)
53 (52.5%)
2/99 (2.0%)
30 (29.7%)
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Results
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Fixed-Dose Hydrocortisone (n= 137)
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Shock-Dependent Hydrocortisone (n= 146)
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No Hydrocortisone (n= 101)
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Median organ support-free days
In-hospital deaths
Median Organ support-free days among survivors
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0 (-1 to 15)
41 (30%)
11.5 (0 to 17)
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0 (-1 to 13)
37 (26%)
9.5 (0 to 16)
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0 (-1 to 11)
33 (33%)
6 (0 to 12)
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Patients with >1 serious adverse events
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4 (3%)
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5 (4%)
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1 (1%)
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Study Author Conclusions
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In patients with severe COVID-19, treatment with a 7 day fixed course of hydrocortisone or shock-dependent dosing of hydrocortisone was 93% and 80% superior, respectively, to no hydrocortisone treatment in improvement of organ support free days. However, this study was stopped early and no statistical superiority was met.
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InpharmD Researcher Critique
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The use of hydrocortisone in patients with severe COVID-19 may be superior to no hydrocortisone treatment in terms of organ support-free days including respiratory and cardiovascular support. These results were reported before meeting any prespecified internal trigger. This trial was open-label and 15% of patients in the “no hydrocortisone” group received systemic corticosteroids.
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