Dexamethasone for COVID-19 – Preliminary Report
Main result
- Population: Of the 11,320 randomized patients, 83% were eligible to be included in the dexamethasone group. Inclusion of 2,104 patients with COVID-19 infection in the dexamethasone group compared to 4,321 in the standard treatment group (control). Other patients were randomized to the other group of the study (not described here).
- Patients characteristics: the average age was 66.1 years with 64% of men, 24% of diabetics, 27% of cardiac pathologies, 21% of chronic pulmonary pathologies, ie 56% with at least significant comorbidity. 82% of patients had an infection confirmed by PCR. 16% received mechanical ventilation.
- Treatment : dexamethasone was received for a median of 6 days with 95% of patients who had at least one dose, but 7% of control group patients also received dexamethasone. The rest of the treatments received were equally divided between the two groups (hydroxychloroquine, lopinavir-ritonavir, anti-IL6 and remdesivir).
- 28-day mortality: was significantly reduced in the dexamethasone group compared to the control arm with an RR = 0.83 (21.6% vs 24.6%, p <0.001). The benefit was greater for the most severe patients, those receiving invasive ventilation with a reduction in mortality of 35% (p <0.001) and 20% for those on non-invasive oxygen therapy (p = 0.002). The benefit has not been demonstrated for non-oxygen-requesting patients.
- Evolution of the disease : dexamethasone has reduced the length of hospital stay (median of 12 days vs 13 days) and has increased the probability of discharge within 28 days with an RR = 1.11 (p = 0.002). Among patients who were not on invasive ventilation, the number of patients progressing to mechanical ventilation or to death was lower in the treatment group with an RR = 0.91 (p = 0.049).
Takeaways
Among patients hospitalized for COVID-19, treatment with dexamethasone has reduced mortality at 28 days in patients on mechanical ventilation by 35% or in oxygen-requiring patients by 20% during hospitalization.
This treatment also seems to reduce the length of hospital stay and reduce the risk of an unfavorable respiratory development for patients who are not severe on admission.
Strength of evidence Strong
- Well conducted randomized controlled trial with significant power
- Preliminary report not giving all the methodological details, however the Recovery study is a large-scale study, carried out by one of the reference teams and the study protocol (on clincicaltrials.gov) is methodologically robust
- Inclusion of COVID-19 suspected patients potentially unconfirmed in the PCR
- Sampling fluctuation with a higher age in the treatment group but adjustment to take into account this potential confounding factor
- Robust statistical models used
- Low rate of missing data but significant variability in the treatment regimen (number of days of treatment)
Objectives
Method
- Study type : adaptive national multicenter open-label randomized controlled trial of 176 hospitals in the UK
- Sample : inclusion of all patients clinically suspected of COVID-19 or confirmed by PCR without treatment-dependant increased risk.
- Data : collection of demographic and clinical-biological data
- Randomization : not stratified with 2: 1 ratio with standard treatment vs 6 mg / day oral or IV dexamethasone for 10 days maximum. There were other treatment group in this study not reported here.
- Follow-up : data collection on discharge from hospital, at the time of death, otherwise 28 days after randomization
- Primary efficacy endpoint = all-cause mortality at 28 days
- Secondary judgments criteria :
- Hospitalization time
- Time before receiving invasive ventilation
- Invasive ventilation (including ECMO)
- Duration of ventilation
- Renal hemodialysis or hemofiltration
- Major cardiac arrhythmia
- Specific cause mortality
- Number of subjects required : ongoing study (in the absence of preliminary data) with a 28-day mortality estimated at 20%, the power would be greater than 90% for a difference of 4% between the groups with 2000 patients (hence the stop of this group)
- Statistics : use of a Cox model to estimate the crude mortality rate with censorship of 4.8% of patients who had not completed their follow-up by June 10. Construction of survival curve (Kaplan-Meier). Analyzes in planned subgroups on age, sex, level of respiratory assistance, the time between the onset of symptoms and the disease as well as the risk of death estimated at 28 days. In these subgroups, comparison by simple Chi2 test to analyze the trend
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