Clinical Summary

Only 1 randomized trial (RECOVERY 2020) identified with available results for dexamethasone treatment for COVID-19¹
Population studied: 6,425 patients hospitalized with COVID-19 (suspected or confirmed) in United Kingdom (176 NHS hospitals) March 19, 2020 to June 8, 2020
Dose studied: Dexamethasone (as oral liquid, oral tablet, or IV preparation) 6 mg once daily for 10 days or until discharge, whichever came sooner (median 7 days)
Data regarding clinical efficacy reported by subgroup

Among patients requiring mechanical ventilation (n=1,007)

Mortality at 28 days may be reduced by an absolute 14.9% (95% CI 7.9% to 20.3%) (Moderate certainty)
Hospital discharge within 28 days may be increased by an absolute 11.2% (95% CI 3.7% to 21.0%) (Moderate certainty)

Among patients requiring oxygen but not mechanical ventilation (n=3,883)

Mortality at 28 days may be reduced by an absolute 4.7% (95% CI 1.6% to 7.3%) (Moderate certainty)
Hospital discharge within 28 days may be increased by an absolute 10.1% (95% CI 4.0% to 16.2%) (Moderate certainty)
Mechanical ventilation or death at 28 days may be reduced by an absolute 4.2% (95% CI 1.3% to 6.7%) (Moderate certainty)

Among patients not requiring respiratory support (n=1,535)

Evidence does not suggest a reduction in mortality at 28 days (risk difference +2.7%, 95% CI -1.3% to +7.7%) (Moderate certainty)
Hospital discharge within 28 days may not be increased (risk difference -3.2%, 95% CI -12.1% to +6.4%) (Low certainty)
Evidence does not suggest a reduction in mechanical ventilation or death at 28 days (risk difference +2.9%, 95% CI -0.8% to +7.6%) (Moderate certainty)

No other randomized trials in patients with COVID-19 with results identified for dexamethasone, but a small partially randomized trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia (reported in preprint) found a reduction in the composite endpoint of death, intensive care unit admission, or requirement of non-invasive ventilation.²
The NIH COVID-19 Treatment Guidelines ³
- recommend dexamethasone (6 mg per day for up to 10 days) for patients with COVID-19 who are mechanically ventilated (AI).
- recommend dexamethasone (6 mg per day for up to 10 days) for patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI).
- recommend against dexamethasone for patients with COVID-19 who do not require supplemental oxygen (AI).

Summary of Findings

Outcome Subgroup	Sample size (# trials, # participants, # events)	Result without dexamethasone	Result with dexamethasone	Effect estimate (dexamethasone effect)	Certainty of finding (Quality of evidence)	What this means
Mortality at 28 days Subgroup who required mechanical ventilation	1 trial, 1,007 participants, 378 events	414 out of 1,000 (41.4%)	265 out of 1,000 (26.5%) 95% CI 211 to 335 out of 1,000 (21.1% to 33.5%)	Age-adjusted rate ratio 0.64 (95% CI 0.51 to 0.81) Age-adjusted risk difference -14.9% (95% CI -20.3% to -7.9%) 149 fewer out of 1,000 (95% CI 203 fewer to 79 fewer out of 1,000)	Moderate certainty due to risk of bias	Dexamethasone may reduce mortality in hospitalized patients with COVID-19 who require mechanical ventilation
Mortality at 28 days Subgroup who required oxygen	1 trial, 3,883 participants, 980 events	262 out of 1,000 (26.2%)	215 out of 1,000 (21.5%) 95% CI 189 to 246 out of 1,000 (18.9% to 24.6%)	Age-adjusted rate ratio 0.82 (95% CI 0.72 to 0.94) Age-adjusted risk difference -4.7% (95% CI -7.3% to -1.6%) 47 fewer out of 1,000 (95% CI 73 fewer to 16 fewer out of 1,000)	Moderate certainty due to risk of bias	Dexamethasone may reduce mortality in hospitalized patients with COVID-19 who require oxygen
Mortality at 28 days Subgroup who did not require respiratory support	1 trial, 1,535 participants, 234 events	140 out of 1,000 (14.0%)	167 out of 1,000 (16.7%) 95% CI 127 to 217 out of 1,000 (12.7% to 21.7%)	Age-adjusted rate ratio 1.19 (95% CI 0.91 to 1.55) Age-adjusted risk difference +2.7% (95% CI -1.3% to +7.7%) 27 more out of 1,000 (95% CI 13 fewer to 77 more out of 1,000)	Moderate certainty due to risk of bias	Available evidence does not suggest dexamethasone helps prevent death in patients hospitalized with COVID-19 who do not require respiratory support
Hospital discharge within 28 days Subgroup who required mechanical ventilation	1 trial, 1,007 participants, 266 events	233 out of 1,000 (23.3%)	345 out of 1,000 (34.5%) 95% CI 270 to 443 out of 1,000 (26.8% to 43.8%)	Age-adjusted rate ratio 1.48 (95% CI 1.16 to 1.90) Age-adjusted risk difference 11.2% (95% CI 3.7% to 21.0%) 112 more out of 1,000 (95% CI 37 more to 210 more out of 1,000)	Moderate certainty due to risk of bias	Dexamethasone may increase the chance of hospital discharge within 28 days in hospitalized patients with COVID-19 who require mechanical ventilation
Hospital discharge within 28 days Subgroup who required oxygen	1 trial, 3,883 participants, 2,676 events	674 out of 1,000 (67.4%)	775 out of 1,000 (77.5%) 95% CI 714 to 836 out of 1,000 (71.4% to 83.6%)	Age-adjusted rate ratio 1.15 (95% CI 1.06 to 1.24) Age-adjusted risk difference 10.1% (95% CI 4.0% to 16.2%) 101 more out of 1,000 (95% CI 40 more to 162 more out of 1,000)	Moderate certainty due to risk of bias	Dexamethasone may increase the chance of hospital discharge within 28 days in hospitalized patients with COVID-19 who require oxygen
Hospital discharge within 28 days Subgroup who did not require respiratory support	1 trial, 1,535 participants, 1,216 events	804 out of 1,000 (80.4%)	772 out of 1,000 (77.2%) 95% CI 683 to 868 out of 1,000 (68.3% to 86.8%)	Age-adjusted rate ratio 0.96 (95% CI 0.85 to 1.08) Age-adjusted risk difference -3.2% (95% CI -12.1% to +6.4%) 32 fewer out of 1,000 (95% CI 121 fewer to 64 more out of 1,000)	Low certainty due to risk of bias and imprecision	Dexamethasone may not improve the chance of hospital discharge within 28 days in hospitalized patients with COVID-19 who do not require respiratory support
Mechanical ventilation or ECMO or death at 28 days Subgroup who required oxygen	1 trial, 3,883 participants, 1,193 events	320 out of 1,000 (32.0%)	278 out of 1,000 (27.8%) 95% CI 253 to 333 out of 1,000 (25.3% to 33.3%)	Age-adjusted risk ratio 0.87 (95% CI 0.79 to 0.96) Age-adjusted risk difference -4.2% (95% CI -6.7% to -1.3%) 42 fewer out of 1,000 (95% CI 67 fewer to 13 fewer out of 1,000)	Moderate certainty due to risk of bias	Dexamethasone may decrease the chance of needing mechanical ventilation or dying in hospitalized patients with COVID-19 who require oxygen
Mechanical ventilation or ECMO or death at 28 days Subgroup who did not require respiratory support	1 trial, 1,535 participants, 257 events	155 out of 1,000 (15.5%)	184 out of 1,000 (18.4%) 95% CI 147 to 231 out of 1,000 (14.7% to 23.1%)	Age-adjusted risk ratio 1.19 (95% CI 0.95 to 1.49) Age-adjusted risk difference +2.9% (95% CI -0.8% to +7.6%) 29 more out of 1,000 (95% CI 8 fewer to 76 more out of 1,000)	Moderate certainty due to risk of bias	Available evidence does not suggest dexamethasone helps prevent needing mechanical ventilation or dying in patients hospitalized with COVID-19 who do not require respiratory support

Summary of Individual Trials

	RECOVERY 2020¹
Dose	Dexamethasone 6 mg once daily for up to 10 days
Population	COVID-19 (suspected or confirmed) and hospitalized - any age
Observed cohort	patients in United Kingdom (176 NHS hospitals) March 19, 2020 to June 8, 2020
Subgroup	Subgroup requiring mechanical ventilation	Subgroup requiring oxygen but not mechanical ventilation	Subgroup not requiring respiratory support
Risk of Bias	Moderate risk of bias	Moderate risk of bias	Moderate risk of bias
Allocation concealment absent or unclear	no concern	no concern	no concern
Blinding incomplete or unclear	Concern	Concern	Concern
Intention-to-treat analysis incomplete or unclear	no concern	no concern	no concern
Baseline imbalance	no concern	no concern	no concern
Subgroup analysis	Concern	Concern	Concern
Early trial termination	no concern	no concern	no concern
Pre-final publication form	no concern	no concern	no concern
Preliminary analysis	no concern	no concern	no concern
Outcomes
Mortality at 28 days	95/324 (29.3%) vs. 283/683 (41.4%) Age-adjusted rate ratio 0.64 (95% CI 0.51 to 0.81) Age-adjusted risk difference -14.9% (95% CI -20.3% to -7.9%)	298/1279 (23.3%) vs. 682/2604 (26.2%) Age-adjusted rate ratio 0.82 (95% CI 0.72 to 0.94) Age-adjusted risk difference -4.7% (95% CI -7.3% to -1.6%)	89/501 (17.8%) vs. 145/1034 (14.0%) Age-adjusted rate ratio 1.19 (95% CI 0.91 to 1.55) Age-adjusted risk difference +2.7% (95% CI -1.3% to +7.7%)
Hospital discharge within 28 days	107/324 (33.0%) vs. 159/683 (23.3%) Age-adjusted rate ratio 1.48 (95% CI 1.16 to 1.90) Age-adjusted risk difference 11.2% (95% CI 3.7% to 21.0%)	921/1279 (72.0%) vs. 1755/2604 (67.4%) Age-adjusted rate ratio 1.15 (95% CI 1.06 to 1.24) Age-adjusted risk difference 10.1% (95% CI 4.0% to 16.2%)	385/501 (76.8%) vs. 831/1034 (80.4%) Age-adjusted rate ratio 0.96 (95% CI 0.85 to 1.08) Age-adjusted risk difference -3.2% (95% CI -12.1% to +6.4%)
Mechanical ventilation or ECMO or death at 28 days	Not reported	359/1279 (28.1%) vs. 834/2604 (32.0%) Age-adjusted risk ratio 0.87 (95% CI 0.79 to 0.96) Age-adjusted risk difference -4.2% (95% CI -6.7% to -1.3%)	97/501 (19.4%) vs. 160/1034 (15.5%) Age-adjusted risk ratio 1.19 (95% CI 0.95 to 1.49) Age-adjusted risk difference +2.9% (95% CI -0.8% to +7.6%)
Adverse events (any)

References

Horby P, Lim WS, Emberson JR, et al for The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17. doi: https://doi.org/10.1056/NEJMoa2021436
Corral L et al. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv 2020 Jun 18;[Preprint]. https://www.medrxiv.org/content/10.1101/2020.06.17.20133579v1
NIH COVID-19 Treatment Guidelines – Corticosteroids (Including Dexamethasone) section last updated July 17, 2020

Cite As

Alper BS, Mayer M, Shahin K. Dexamethasone Treatment for COVID-19: Clinical Outcomes Results Extracted from Randomized Controlled Trials. COVID-19 Knowledge Accelerator Evidence Reports, entry 28, version 2020-07-20. Created 2020 Jun 22. Revised 2020 Jul 20. Available at: https://gps.health/coka/reports/EvidenceReport/28. Computable resource at: https://gps.health/coka/resources/EvidenceReport/28?version=8

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