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Dexamethasone for COVID-19 – Preliminary Report
1
Effect of Dexamethasone in Hospitalized Patients with
COVID-19 – Preliminary Report
Running title: Dexamethasone for COVID-19 – Preliminary Report
RECOVERY Collaborative Group*
*The writing committee and trial steering committee are listed at the end of this manuscript and
a complete list of collaborators in the Randomised Evaluation of COVID-19 Therapy
(RECOVERY) trial is provided in the Supplementary Appendix.
Correspondence to: Dr Peter W Horby and Dr Martin J Landray, RECOVERY Central
Coordinating Office, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3
7LF, United Kingdom.
Email: recoverytrial@ndph.ox.ac.uk
Word count:
Abstract – 250 words
Main text – 2820
References – 40
Tables & Figures – 2 + 2
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Dexamethasone for COVID-19 – Preliminary Report
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ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage.
Corticosteroids may modulate immune-mediated lung injury and reducing progression to
respiratory failure and death.
Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a
randomized, controlled, open-label, adaptive, platform trial comparing a range of possible
treatments with usual care in patients hospitalized with COVID-19. We report the preliminary
results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual
care alone. The primary outcome was 28-day mortality.
Results: 2104 patients randomly allocated to receive dexamethasone were compared with
4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated
dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-
adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The
proportional and absolute mortality rate reductions varied significantly depending on level of
respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths
by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65
[95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive
mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not
reduce mortality in patients not receiving respiratory support at randomization (17.0% vs.
13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).
Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day
mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but
not among patients not receiving respiratory support.
Trial registrations: The RECOVERY trial is registered with ISRCTN (50189673) and
clinicaltrials.gov (NCT04381936).
Funding: Medical Research Council and National Institute for Health Research (Grant ref:
MC_PC_19056).
Keywords: COVID-19, dexamethasone, clinical trial.
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Dexamethasone for COVID-19 – Preliminary Report
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INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus
disease 2019 (COVID-19), emerged in China in late 2019 from a zoonotic source.1 The majority
of COVID-19 infections are either asymptomatic or result in only mild disease. However, a
substantial proportion of older infected individuals develop a respiratory illness requiring hospital
care,2 which can progress to critical illness with hypoxemic respiratory failure requiring
prolonged ventilatory support.3-6 Amongst COVID-19 patients admitted to UK hospitals, the case
fatality rate is over 26%, and is over 37% in patients requiring invasive mechanical ventilation.7
Although remdesivir has been shown to shorten the time to recovery in hospitalized patients,8
no therapeutic agents have been shown to reduce mortality.
The pathophysiology of severe COVID-19 is dominated by an acute pneumonic process with
extensive radiological opacity and, on autopsy, diffuse alveolar damage, inflammatory infiltrates
and microvascular thromobosis.9,10 The host immune response is thought to play a key role in
the pathophysiology of organ failure in other severe viral pneumonias such as highly pathogenic
avian influenza,11 severe acute respiratory syndrome (SARS),12,13 and pandemic and seasonal
influenza.14 Inflammatory organ injury may occur in severe COVID-19, with a subset of patients
having markedly elevated inflammatory markers such as C-reactive protein, ferritin, and
interleukins 1 and 6.6,15,16 Several therapeutic interventions to mitigate inflammatory organ injury
have been proposed in viral pneumonia but the value of corticosteroids has been widely
debated.17,18
In the absence of reliable evidence from large-scale randomized clinical trials, there is great
uncertainty about the effectiveness of corticosteroids in COVID-19. Prior to RECOVERY, many
COVID-19 treatment guidelines stated that corticosteroids were either ‘contraindicated’ or ‘not
recommended’19 although in China, corticosteroids are recommended for severe cases.20
Practice has varied widely across the world: in some series, as many as 50% of cases were
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treated with corticosteroids.21,22 Here we report the results of a randomized controlled trial of
dexamethasone in patients hospitalized with COVID-19.
METHODS
Trial design and participants
The RECOVERY trial is an investigator-initiated, individually randomized, controlled, open-label,
adaptive platform trial to evaluate the effects of potential treatments in patients hospitalized with
COVID-19. The trial was conducted at 176 National Health Service (NHS) hospital organizations
in the United Kingdom (see Supplementary Appendix), supported by the National Institute for
Health Research Clinical Research Network. The trial was coordinated by the Nuffield
Department of Population Health at University of Oxford, the trial sponsor.
Hospitalized patients were eligible for the trial if they had clinically suspected or laboratory
confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the
attending clinician, put the patient at significant risk if they were to participate in the trial. Initially,
recruitment was limited to patients aged at least 18 years but the age limit was removed from 9
May 2020. Pregnant or breast-feeding women were eligible.
Written informed consent was obtained from all patients or from a legal representative if they
were too unwell or unable to provide consent. The trial was conducted in accordance with the
principles of the International Conference on Harmonization–Good Clinical Practice guidelines
and approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) and
the Cambridge East Research Ethics Committee (ref: 20/EE/0101). The protocol and statistical
analysis plan are available on the study website www.recoverytrial.net.
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Randomization
Baseline data collected using a web-based case report form included demographics, level of
respiratory support, major comorbidities, suitability of the study treatment for a particular patient
and treatment availability at the study site. Eligible and consenting patients were assigned in a
ratio of 2:1 to either usual standard of care or to usual standard of care plus dexamethasone 6
mg once daily (oral or intravenous) for up to 10 days (or until discharge if sooner) or to one of
the other suitable and available treatment arms (see Supplementary Appendix) using web-
based simple randomization with allocation concealment. For some patients, dexamethasone
was either unavailable at the hospital at the time of enrolment or considered by the managing
doctor to be either definitely indicated or definitely contraindicated. These patients were
excluded from entry in the randomized comparison of dexamethasone vs. usual care and hence
are not part of this report. The randomly assigned treatment was prescribed by the treating
clinician. Participants and local study staff were not blinded to the allocated treatment.
Procedures
A single online follow-up form was to be completed when participants were discharged, had
died or at 28 days after randomization (whichever occurred earlier). Information was recorded
on adherence to allocated study treatment, receipt of other study treatments, duration of
admission, receipt of respiratory or renal support, and vital status (including cause of death). In
addition, routine health care and registry data were obtained including information on vital status
(with date and cause of death); discharge from hospital; intensive care use; and renal
replacement therapy.
Outcome measures
The primary outcome was all-cause mortality within 28 days of randomization. Secondary
outcomes were time to discharge from hospital, and among patients not receiving invasive
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mechanical ventilation at randomization, subsequent receipt of invasive mechanical ventilation
(including extra-corporeal membrane oxygenation) or death. Subsidiary clinical outcomes
included cause-specific mortality, receipt of renal hemodialysis or hemofiltration, major cardiac
arrhythmia (recorded in a subset), and receipt and duration of ventilation.
Statistical Analysis
For the primary outcome of 28-day mortality, the hazard ratio from Cox regression was used to
estimate the mortality rate ratio. The few patients (4.8%) who had not been followed for 28 days
by the time of the data cut (10 June 2020) were either censored on 8 June 2020 or, if they had
already been discharged alive, were right-censored at day 29 (that is, in the absence of any
information to the contrary they were assumed to have survived 28 days). Kaplan-Meier survival
curves were constructed to display cumulative mortality over the 28-day period. Cox regression
was used to analyze the secondary outcome of hospital discharge within 28 days, with patients
who died in hospital right-censored on day 29. For the pre-specified composite secondary
outcome of invasive mechanical ventilation or death within 28 days (among those not receiving
invasive mechanical ventilation at randomization), the precise date of invasive mechanical
ventilation was not available and so a log-binomial regression model was used to estimate the
risk ratio.
Pre-specified analyses of the primary outcome were performed in five subgroups defined by
characteristics at randomization: age, sex, level of respiratory support, days since symptom
onset, and predicted 28-day mortality risk. Observed effects within subgroup categories were
compared using a chi-square test for trend. Through the play of chance in the unstratified
randomization, mean age was 1.1 years higher in those allocated dexamethasone than those
allocated usual care (Table 1). To account for this imbalance in an important prognostic factor,
the estimates of rate ratios and risk ratios (both hereon denoted RR) were adjusted for baseline
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Dexamethasone for COVID-19 – Preliminary Report
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age. This adjustment was not specified in the first version of the statistical analysis plan, but
was added once the imbalance in age (a key prognostic factor) became apparent. Results with
and without age-adjustment are provided and show that it does not alter the conclusions
materially.
Estimates of rate and risk ratios are shown with 95% confidence intervals. All p-values are 2-
sided and all analyses were done according to the intention-to-treat principle. The full database
is held by the study team which collected the data from study sites and performed the analyses
at the Nuffield Department of Population Health, University of Oxford.
Sample size and decision to stop enrolment
As stated in the protocol, appropriate sample sizes could not be estimated when the trial was
being planned at the start of the COVID-19 pandemic. As the trial progressed, the trial Steering
Committee, blinded to the results of the study treatment comparisons, formed the view that, if
28-day mortality was 20% then a comparison of at least 2000 patients allocated to active drug
and 4000 to usual care alone would yield at least 90% power at two-sided P=0.01 to detect a
clinically relevant absolute difference of 4 percentage points between the two groups (a
proportional reduction of one-fifth). Consequently, on 8 June 2020, the Steering Committee
closed recruitment to the dexamethasone arm since enrolment exceeded 2000 patients.
RESULTS
Patients
Of the 11,320 patients randomized between 19 March and 8 June, 9355 (83%) were eligible to
be randomized to dexamethasone (that is dexamethasone was available in the hospital at the
time and the patient had no known indication for or contraindication to dexamethasone). Of
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Dexamethasone for COVID-19 – Preliminary Report
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these, 2104 were randomized to dexamethasone and 4321 were randomized to usual care
(Figure S1), with the remainder being randomized to one of the other treatment arms. Mean age
of study participants in this comparison was 66.1 years (Table 1) and 36% patients were female.
A history of diabetes was present in 24% of patients, heart disease in 27%, and chronic lung
disease in 21%, with 56% having at least one major comorbidity recorded. In this analysis, 82%
of patients had laboratory confirmed SARS-CoV-2 infection, with the result currently awaited for
9%. At randomization, 16% were receiving invasive mechanical ventilation or extracorporeal
membrane oxygenation, 60% were receiving oxygen only (with or without non-invasive
ventilation), and 24% were receiving neither.
Follow-up information was complete for 6119 (95%) of the randomized patients. Of those
allocated to dexamethasone 95% received at least 1 dose (Table S1) and the median number of
days of treatment was 6 days. 7% of the usual care group received dexamethasone. Use of
azithromycin during the follow-up period was similar in both arms (23% vs. 24%) and very few
patients received hydroxychloroquine, lopinavir-ritonavir, or interleukin-6 antagonists during
follow-up (Table S1). Remdesivir only became available for use in the UK under the MHRA
Emergency Access to Medicines Scheme on 26 May 2020.
Primary outcome
Significantly fewer patients allocated to dexamethasone met the primary outcome of 28-day
mortality than in the usual care group (454 of 2104 patients [21.6%] allocated dexamethasone
vs. 1065 of 4321 patients [24.6%] allocated usual care; rate ratio, 0.83; 95% confidence interval
[CI], 0.74 to 0.92; P<0.001) (Figure 1A). In a pre-specified subgroup analysis by level of
respiratory support received at randomization, there was a significant trend showing the
greatest absolute and proportional benefit among those patients receiving invasive mechanical
ventilation at randomization (test for trend p<0.001) (Figure 2). Dexamethasone reduced 28-day
mortality by 35% in patients receiving invasive mechanical ventilation (rate ratio 0.65 [95% CI
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Dexamethasone for COVID-19 – Preliminary Report
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0.51 to 0.82]; p<0.001) and by 20% in patients receiving oxygen without invasive mechanical
ventilation (rate ratio 0.80 [95% CI 0.70 to 0.92]; p=0.002) (Figure 1B-C). However, there was
no evidence of benefit among those patients who were not receiving respiratory support (rate
ratio 1.22 [95% CI 0.93 to 1.61]; p=0.14) (Figure 1D). Sensitivity analyses without age-
adjustment produced similar findings (Table S2).
Patients on invasive mechanical ventilation at randomization were on average 10 years younger
than those not receiving any respiratory support and had symptoms prior to randomization for 7
days longer (Table 1). 28-day mortality in the usual care group was highest in those who were
receiving invasive mechanical ventilation at randomization (40.7%), intermediate in those
patients who received oxygen only (25.0%), and lowest among those who were not receiving
respiratory support at randomization (13.2%). Consequently, the greatest absolute reductions in
28-day mortality were seen among those patients on invasive mechanical ventilation.
Patients with longer duration of symptoms (who were more likely to be on invasive mechanical
ventilation at randomization) had a greater mortality benefit, such that dexamethasone was
associated with a reduction in 28-day mortality among those with symptoms for more than 7
days but not among those with more recent symptom onset (test for trend p<0.001) (Figure S2).
Secondary outcomes
Allocation to dexamethasone was associated with a shorter duration of hospitalization than
usual care (median 12 days vs. 13 days) and a greater probability of discharge within 28 days
(rate ratio 1.11 [95% CI 1.04 to 1.19]; p=0.002) (Table 2) with the greatest effect seen among
those receiving invasive mechanical ventilation at baseline (test for trend p=0.002) (Figure S3a).
Among those not on invasive mechanical ventilation at baseline, the number of patients
progressing to the pre-specified composite secondary outcome of invasive mechanical
ventilation or death was lower among those allocated to dexamethasone (risk ratio 0.91 [95% CI
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Dexamethasone for COVID-19 – Preliminary Report
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0.82 to 1.00]; p=0.049) (Table 2) but with significantly greater effects among patients receiving
oxygen at randomization (test for trend p=0.008) (Figure S3b).
Subsidiary clinical outcomes
The risk of progression to invasive mechanical ventilation was lower among those allocated
dexamethasone vs. usual care (risk ratio 0.76 [95% CI 0.61 to 0.96]; p=0.021) (Table 2).
Preliminary analyses indicate no excess risk of any particular cause of death (in particular there
was no excess of deaths due to non-COVID infection). More detailed analyses of cause-specific
mortality, need for renal dialysis or hemofiltration, and duration of ventilation are in preparation.
DISCUSSION
These preliminary results show that dexamethasone 6mg per day for up to 10 days reduces 28-
day mortality in COVID-19 patients receiving invasive mechanical ventilation by one third, and
by one fifth in patients receiving oxygen without invasive mechanical ventilation. Similarly,
benefit was clearer in patients treated more than 7 days after treatment onset, when
inflammatory lung damage is likely to have been more common. However, no benefit was
demonstrated in hospitalized COVID-19 patients who were not receiving respiratory support and
the results are consistent with possible harm in this group.
RECOVERY is a large, pragmatic, randomized, controlled adaptive platform trial designed to
provide rapid and robust assessment of the impact of readily available potential treatments for
COVID-19 on 28-day mortality. Around 15% of all UK hospitalized patients with COVID-19 were
enrolled in the trial and the control arm fatality rate is consistent with the overall hospitalized
case fatality rate in the UK.7 Only essential data were collected at hospital sites with additional
information (including long-term mortality) ascertained through linkage with routine data
sources. We did not collect information on physiological, laboratory or virologic parameters. The
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protocol combines the methods of large, simple trials of treatments for acute myocardial
infarction in the 1980s with the opportunities provided by digital health care in the 2020s.23-25 It
has progressed at unprecedented speed, as is essential for studies during epidemics.26 These
preliminary results for dexamethasone were announced on 16 June 2020, just 98 days after the
protocol was first drafted, and were adopted into UK practice later the same day.27
Corticosteroids have been widely used in syndromes closely related to COVID-19, including
SARS, MERS, severe influenza, and community acquired pneumonia. However, the evidence to
support or discourage the use of corticosteroids in these conditions has been very weak due to
the lack of sufficiently powered randomized controlled trials.28-31 In addition, the evidence base
has suffered from heterogeneity in corticosteroid doses, medical conditions, and disease
severity studied. It is likely that the beneficial effect of corticosteroids in severe viral respiratory
infections is dependent on using the right dose, at the right time, in the right patient. High doses
may be more harmful than helpful, as may corticosteroid treatment given at a time when control
of viral replication is paramount and inflammation is minimal. Slower clearance of viral RNA has
been observed in patients with SARS, MERS and influenza treated with systemic corticosteroids
but the clinical significance of this is unknown.29,32,33 Unlike SARS, where viral replication peaks
in the second week of illness,34 peak viral shedding in COVID-19 appears to be higher early in
the illness and declines thereafter.35-38 The greater mortality benefit of dexamethasone in
patients with COVID-19 who required respiratory support, and among those recruited after the
first week of their illness, suggests that at this stage the disease is dominated by
immunopathology, with active virus replication playing a secondary role. It is also possible there
is an effect via mineralocorticoid receptor binding in the context of SARS-CoV-2 induced
dysregulation of the renin-angiotensin system.39 This would caution against extrapolating the
effect of dexamethasone in patients with COVID-19 to patients with other viral respiratory
diseases that have a different natural history.
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The RECOVERY trial provides clear evidence that treatment with dexamethasone 6 mg once
daily for up to 10 days reduces 28-day mortality in patients with COVID-19 who are receiving
respiratory support. Based on these results, 1 death would be prevented by treatment of around
8 patients requiring invasive mechanical ventilation or around 25 patients requiring oxygen
(which, in the UK, is recommended when oxygen saturations on room air are 92-94%)40 without
invasive mechanical ventilation. There was no benefit (and the possibility of harm) among
patients who did not require oxygen. Prior to the completion of this trial, many COVID-19
treatment guidelines have stated that corticosteroids are either ‘contraindicated’ or ‘not
recommended’ in COVID-19.19 These should now be updated, as has already happened within
the UK.27 Dexamethasone provides an effective treatment for the sickest patients with COVID-
19 and, given its low cost, well understood safety profile, and widespread availability, is one that
can be used worldwide.
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Dexamethasone for COVID-19 – Preliminary Report
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Authorship
This manuscript was prepared by the Writing Committee and reviewed and approved by all
members of the trial Steering Committee. The funders had no role in the analysis of the data,
preparation and approval of this manuscript, or the decision to submit it for publication. The first
and last members of the Writing Committee vouch for the data and analyses, and for the fidelity
of this report to the study protocol and data analysis plan.
Writing Committee (on behalf of the RECOVERY Collaborative Group):
Peter Horby FRCP,a,* Wei Shen Lim FRCP,b,* Jonathan Emberson PhD,c,d Marion Mafham MD,c
Jennifer Bell MSc,c Louise Linsell DPhil,c Natalie Staplin PhD,c,d Christopher Brightling
FMedSci,e Andrew Ustianowski PhD,f Einas Elmahi MPhil,g Benjamin Prudon FRCP,h
Christopher Green DPhil,i Timothy Felton PhD,j David Chadwick PhD,k Kanchan Rege
FRCPath,l Christopher Fegan MD,m Lucy C Chappell PhD,n Saul N Faust FRCPCH,o Thomas
Jaki PhD,p,q Katie Jeffery PhD,r Alan Montgomery PhD,s Kathryn Rowan PhD,t Edmund
Juszczak PhD,c J Kenneth Baillie MD PhD,u Richard Haynes DM,c,d† Martin J Landray PhD.c,d,v†
a Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
b Respiratory Medicine Department, Nottingham University Hospitals NHS Trust, Nottingham,
United Kingdom
c Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
d MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom
e Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester,
Leicester, United Kingdom
f Regional Infectious Diseases Unit, North Manchester General Hospital & University of
Manchester, Manchester, United Kingdom
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g Research and Development Department, Northampton General Hospital, Northampton, United
Kingdom
h Department of Respiratory Medicine, North Tees & Hartlepool NHS Foundation Trust,
Stockton-on-Tees, United Kingdom
i University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology &
Infection, University of Birmingham, Birmingham, United Kingdom
j University of Manchester and Manchester University NHS Foundation Trust, Manchester,
United Kingdom
k Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, United Kingdom
l North West Anglia NHS Foundation Trust, Peterborough, United Kingdom
m Department of Research and Development, Cardiff and Vale University Health Board, Cardiff,
United Kingdom
n School of Life Course Sciences, King’s College London, London, United Kingdom
o NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University
Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton,
United Kingdom
p Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom
q MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
r Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
s School of Medicine, University of Nottingham, Nottingham, United Kingdom
t Intensive Care National Audit & Research Centre, London, United Kingdom
u Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom
v NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust,
Oxford, United Kingdom
*,† equal contribution
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Dexamethasone for COVID-19 – Preliminary Report
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Data Monitoring Committee
Peter Sandercock, Janet Darbyshire, David DeMets, Robert Fowler, David Lalloo, Ian Roberts,
Janet Wittes.
Acknowledgements
We would like to thank the many thousands of doctors, nurses, pharmacists, other allied health
professionals, and research administrators at 176 NHS hospital organizations across the whole
of the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public
Health England, Department of Health & Social Care, the Intensive Care National Audit &
Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure
Anonymised Information Linkage (SAIL) at University of Swansea, and the NHS in England,
Scotland, Wales and Northern Ireland. We would especially like to thank the members of the
independent Data Monitoring Committee. But above all, we would like to thank the thousands of
patients who participated in this study.
Funding
The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and
Innovation/National Institute for Health Research (NIHR) (Grant reference: MC_PC_19056) and
by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and
Melinda Gates Foundation, the Department for International Development, Health Data
Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health
Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support
Funding. WSL is supported by core funding provided by NIHR Nottingham Biomedical Research
Centre. TJ received funding from UK Medical Research Council (MC_UU_0002/14). This report
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Dexamethasone for COVID-19 – Preliminary Report
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is independent research arising in part from Prof Jaki’s Senior Research Fellowship (NIHR-
SRF-2015-08-001) supported by the National Institute for Health Research.
The views expressed in this publication are those of the authors and not necessarily those of
the NHS, the National Institute for Health Research or the Department of Health and Social
Care (DHCS).
Conflicts of interest
The authors have no conflict of interest or financial relationships relevant to the submitted work
to disclose. No form of payment was given to anyone to produce the manuscript. All authors
have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
The Nuffield Department of Population Health at the University of Oxford has a staff policy of not
accepting honoraria or consultancy fees directly or indirectly from industry (see
https://www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-policy-jun-20.pdf).
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Dexamethasone for COVID-19 – Preliminary Report
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References
1. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019.
N Engl J Med 2020.
2. Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-
based analysis. Lancet Infect Dis 2020; 20(6): 669-77.
3. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-
19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
4. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020.
5. Cao J, Tu WJ, Cheng W, et al. Clinical Features and Short-term Outcomes of 102 Patients with
Corona Virus Disease 2019 in Wuhan, China. Clin Infect Dis 2020.
6. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on
an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020.
7. Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19
using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.
Bmj 2020; 369: m1985.
8. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Preliminary
Report. N Engl J Med 2020.
9. Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, et al. Pathological evidence of pulmonary
thrombotic phenomena in severe COVID-19. J Thromb Haemost 2020.
10. Carsana L, Sonzogni A, Nasr A, et al. Pulmonary post-mortem findings in a series of COVID-19 cases
from northern Italy: a two-centre descriptive study. Lancet Infect Dis 2020.
11. de Jong MD, Simmons CP, Thanh TT, et al. Fatal outcome of human influenza A (H5N1) is associated
with high viral load and hypercytokinemia. Nat Med 2006; 12(10): 1203-7.
12. Cameron MJ, Ran L, Xu L, et al. Interferon-mediated immunopathological events are associated
with atypical innate and adaptive immune responses in patients with severe acute respiratory
syndrome. J Virol 2007; 81(16): 8692-706.
13. Wong CK, Lam CW, Wu AK, et al. Plasma inflammatory cytokines and chemokines in severe acute
respiratory syndrome. Clin Exp Immunol 2004; 136(1): 95-103.
14. Baillie JK, Digard P. Influenza--time to target the host? N Engl J Med 2013; 369(2): 191-3.
15. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in
Wuhan, China. Lancet 2020.
16. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473-4.
17. Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet
2020; 395(10225): 683-4.
18. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for
2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
19. Dagens A, Sigfrid L, Cai E, et al. Scope, quality, and inclusivity of clinical guidelines produced early in
the covid-19 pandemic: rapid review. Bmj 2020; 369: m1936.
20. Zhao JP, Hu Y, Du RH, et al. [Expert consensus on the use of corticosteroid in patients with 2019-
nCoV pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(3): 183-4.
21. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel
Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020.
22. Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel
coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020; 368: m606.
23. Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Stat Med 1984;
3(4): 409-22.
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
Dexamethasone for COVID-19 – Preliminary Report
18
24. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of
suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival)
Collaborative Group. Lancet 1988; 2(8607): 349-60.
25. Collins R, Bowman L, Landray M, Peto R. The Magic of Randomization versus the Myth of Real-
World Evidence. N Engl J Med 2020; 382(7): 674-8.
26. Rojek AM, Horby PW. Modernising epidemic science: enabling patient-centred research during
epidemics. BMC Med 2016; 14(1): 212.
27. NHS. Dexamethasone in the treatment of COVID-19: Implementation and management of supply
for treatment in hospitals. 2020.
https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103054
(accessed 20 June 2020).
28. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med 2006;
3(9): e343.
29. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid Therapy for Critically Ill Patients with
Middle East Respiratory Syndrome. Am J Respir Crit Care Med 2018; 197(6): 757-67.
30. Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as
Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and
Meta-analysis. Crit Care Med 2020; 48(2): e98-e106.
31. Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid Therapy for Patients Hospitalized
With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Annals of internal
medicine 2015; 163(7): 519-28.
32. Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-
associated Coronavirus RNA concentrations in adult patients. J Clin Virol 2004; 31(4): 304-9.
33. Lee N, Chan PK, Hui DS, et al. Viral loads and duration of viral shedding in adult patients hospitalized
with influenza. J Infect Dis 2009; 200(4): 492-500.
34. Cheng PK, Wong DA, Tong LK, et al. Viral shedding patterns of coronavirus in patients with probable
severe acute respiratory syndrome. Lancet 2004; 363(9422): 1699-700.
35. To KK, Tsang OT, Leung WS, et al. Temporal profiles of viral load in posterior oropharyngeal saliva
samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort
study. Lancet Infect Dis 2020; 20(5): 565-74.
36. Zhou R, Li F, Chen F, et al. Viral dynamics in asymptomatic patients with COVID-19. Int J Infect Dis
2020; 96: 288-90.
37. He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19.
Nat Med 2020; 26(5): 672-5.
38. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with
COVID-2019. Nature 2020; 581(7809): 465-9.
39. Liaudet L, Szabo C. Blocking mineralocorticoid receptor with spironolactone may have a wide range
of therapeutic actions in severe COVID-19 disease. Crit Care 2020; 24(1): 318.
40. NHS. Clinical guide for the optimal use of Oxygen therapy during the coronavirus pandemic. 2020.
https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/04/C0256-specialty-
guide-oxygen-therapy-and-coronavirus-9-april-2020.pdf.
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
Dexamethasone for COVID-19 – Preliminary Report
19
Table and figures
Table 1: Baseline characteristics by randomized allocation and level of respiratory
support received
Results are count (%), mean ± standard deviation, or median (inter-quartile range). * Includes 6
pregnant women. † SARS-Cov-2 test results are captured on the follow-up form, so are
currently unknown for some patients. There was a significant difference (2p=0.008) in mean age
of 1.1 years between those randomly allocated dexamethasone and those randomly allocated
usual care but no significant differences between these groups in any other baseline
characteristic. The ‘oxygen only’ group includes non-invasive ventilation.
Table 2: Effect of allocation to dexamethasone on main study outcomes
RR=Rate Ratio for the outcomes of 28-day mortality and hospital discharge, and risk ratio for
the outcome of receipt of invasive mechanical ventilation or death (and its subcomponents).
Estimates of the RR and its 95% confidence interval are adjusted for age in three categories
(<70 years, 70-79 years, and 80 years or older). * Analyses exclude those on invasive
mechanical ventilation at randomization.
Figure 1: 28−day mortality in all patients (panel a) and separately according to level of
respiratory support received at randomization (panels b-d)
RR=age−adjusted rate ratio. CI=confidence interval. The ‘oxygen only’ group includes non-
invasive ventilation. Note: in the RECOVERY trial press release of 16 June 2020, effects in
subgroups of level of respiratory support received were shown with 99% CIs, not 95% CIs as
inadvertently stated. The age−adjusted rate ratio and 99% confidence intervals remain
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
Dexamethasone for COVID-19 – Preliminary Report
20
unchanged in this analysis: no oxygen required, RR 1.22 (99% CI 0.86−1.75); oxygen only, RR
0.80 (99% CI 0.67−0.96); invasive mechanical ventilation, RR 0.65 (99% CI 0.48−0.88).
Figure 2: Effect of allocation to dexamethasone on 28−day mortality by level of
respiratory support received at randomization
RR=age−adjusted rate ratio. CI=confidence interval. Subgroup−specific RR estimates are
represented by squares (with areas of the squares proportional to the amount of statistical
information) and the horizontal lines through them correspond to the 95% confidence intervals.
The ‘oxygen only’ group includes non-invasive ventilation. Note: in the RECOVERY trial press
release of 16 June 2020, effects in subgroups of level of respiratory support received were
shown with 99% CIs, not 95% CIs as inadvertently stated. The age−adjusted rate ratio and 99%
confidence intervals remain unchanged in this analysis: no oxygen required, RR 1.22 (99% CI
0.86−1.75); oxygen only, RR 0.80 (99% CI 0.67−0.96); invasive mechanical ventilation, RR 0.65
(99% CI 0.48−0.88).
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
Table 1: Baseline characteristics by randomized allocation and level of respiratory support
received
Treatment allocation
Respiratory support received
at randomization
Dexamethasone
(n=2104)
Usual care
(n=4321)
No oxygen
received
(n=1535)
Oxygen only
(n=3883)
Invasive
mechanical
ventilation
(n=1007)
Age, years
66.9 (15.4)
65.8 (15.8)
69.3 (17.6)
66.7 (15.3)
59.0 (11.5)
<70
1142 (54%)
2506 (58%)
660 (43%)
2149 (55%)
839 (83%)
≥70 to <80 467 (22%)
860 (20%)
338 (22%)
837 (22%)
152 (15%)
≥80 495 (24%)
955 (22%)
537 (35%)
897 (23%)
16 (2%)
Sex
Male
1338 (64%)
2750 (64%)
892 (58%)
2462 (63%)
734 (73%)
Female*
766 (36%)
1571 (36%)
643 (42%)
1421 (37%)
273 (27%)
Number of days since symptom onset 8 (5-13)
9 (5-13)
6 (3-10)
9 (5-12)
13 (8-18)
Respiratory support received
No oxygen received
501 (24%)
1034 (24%)
1535 (100%)
0 (0%)
0 (0%)
Oxygen only
1279 (61%)
2604 (60%)
0 (0%)
3883 (100%)
0 (0%)
Invasive mechanical ventilation
324 (15%)
683 (16%)
0 (0%)
0 (0%)
1007 (100%)
Previous diseases
Diabetes 521 (25%)
1025 (24%)
342 (22%)
950 (24%)
254 (25%)
Heart disease
586 (28%)
1171 (27%)
519 (34%)
1074 (28%)
164 (16%)
Chronic lung disease
415 (20%)
931 (22%)
351 (23%)
883 (23%)
112 (11%)
Tuberculosis
6 (<0.5%)
19 (<0.5%)
8 (1%)
11 (<0.5%)
6 (1%)
HIV
12 (1%)
20 (<0.5%)
5 (<0.5%)
21 (1%)
6 (1%)
Severe liver disease
37 (2%)
82 (2%)
32 (2%)
72 (2%)
15 (1%)
Severe kidney impairment
167 (8%)
358 (8%)
120 (8%)
253 (7%)
152 (15%)
Any of the above
1174 (56%)
2417 (56%)
911 (59%)
2175 (56%)
505 (50%)
SARS-Cov-2 test result
Positive
1702 (81%)
3553 (82%)
1198 (78%)
3144 (81%)
913 (91%)
Negative
213 (10%)
397 (9%)
182 (12%)
398 (10%)
30 (3%)
Test result not yet known†
189 (9%)
371 (9%)
155 (10%)
341 (9%)
64 (6%)
Results are count (%), mean ± standard deviation, or median (inter-quartile range). * Includes 6 pregnant women. † SARS-Cov-2 test results
are captured on the follow
-up form, so are currently unknown for some. There was a significant (2p=0.008) difference in mean age between
those allocated dexamethasone and those allocated usual care, but no significant differences between these groups in any othe
r baseline
characteristic. The 'oxygen only' group includes non
-invasive ventilation.
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
Table 2: Effect of allocation to dexamethasone on main study outcomes
Treatment allocation
Dexamethasone
(n=2104)
Usual care
(n=4321)
RR (95% CI)
p-value
Primary outcome:
28-day mortality 454 (21.6%)
1065 (24.6%)
0.83 (0.74-0.92)
<0.001
Secondary outcomes:
Discharged from hospital within 28 days
1360 (64.6%)
2639 (61.1%)
1.11 (1.04-1.19)
0.002
Receipt of invasive mechanical ventilation or death*
425/1780 (23.9%)
939/3638 (25.8%)
0.91 (0.82-1.00)
0.049
Invasive mechanical ventilation
92/1780 (5.2%)
258/3638 (7.1%)
0.76 (0.61-0.96)
0.021
Death
360/1780 (20.2%)
787/3638 (21.6%)
0.91 (0.82-1.01)
0.07
RR=Rate Ratio for the outcomes of 28-day mortality and hospital discharge, and risk ratio for the outcome of receipt of invasive mechanical
ventilation or death (and its subcomponents). Estimates of the RR and its 95% confidence interval are adjusted for age in thr
ee categories
(<70 years , 70
-79 years, and 80 years or older). * Analyses exclude those on invasive mechanical ventilation at randomization.
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
0
10
20
30
40
50
Mortality, %
0 7 14 21 28
Days since randomization
RR 0.83 (95% CI 0.74−0.92)
p<0.001
2104 1860 1670 1595 1547
4321 3700 3329 3154 3053
Number at risk:
Dexamethasone
Usual care
Figure 1: 28−day mortality in all patients (panel a) and separately according
to level of respiratory support received at randomization (panels b−d)
a) All participants (n=6425)
Usual care
Dexamethasone
0
10
20
30
40
50
Mortality, %
0 7 14 21 28
Days since randomization
RR 1.22 (95% CI 0.93−1.61)
p=0.14
501 463 420 394 383
1034 969 890 856 832
b) No oxygen received (n=1535)
Usual care
Dexamethasone
0
10
20
30
40
50
Mortality, %
0 7 14 21 28
Days since randomization
RR 0.80 (95% CI 0.70−0.92)
p=0.002
1279 1107 1004 971 940
2604 2162 1965 1880 1832
Number at risk:
Dexamethasone
Usual care
RR=age−adjusted rate ratio. CI=confidence interval. The 'oxygen only' group includes non−invasive ventilation. Note: in the RECOVERY
trial press release of 16 June 2020, effects in subgroups of level of respiratory support received were shown with 99% CIs, not 95% CIs as
inadvertently stated. The age−adjusted rate ratio and 99% confidence intervals remain unchanged in this analysis: no oxygen required,
RR 1.22 (99% CI 0.86−1.75); oxygen only, RR 0.80 (99% CI 0.67−0.96); invasive mechanical ventilation, RR 0.65 (99% CI 0.48−0.88).
c) Oxygen only (n=3883)
Usual care
Dexamethasone
0
10
20
30
40
50
Mortality, %
0 7 14 21 28
Days since randomization
RR 0.65 (95% CI 0.51−0.82)
p<0.001
324 290 246 230 224
683 569 474 418 389
d) Invasive mechanical ventilation (n=1007)
Usual care
Dexamethasone
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
0.5 0.75 11.5 2
Figure 2: Effect of allocation to dexamethasone on 28−day mortality by level
of respiratory support received at randomization
Dexamethasone Usual care
Respiratory support at
randomization RR (95% CI)
RR=age−adjusted rate ratio. CI=confidence interval. Subgroup−specific RR estimates are represented by squares (with areas of the squares
proportional to the amount of statistical information) and the lines through them correspond to the 95% confidence intervals. The 'oxygen only'
group includes non−invasive ventilation. Note: in the RECOVERY trial press release of 16 June 2020, effects in subgroups of level of respiratory
support received were shown with 99% CIs, not 95% CIs as inadvertently stated. The age−adjusted rate ratio and 99% confidence intervals remain
unchanged in this analysis: no oxygen required, RR 1.22 (99% CI 0.86−1.75); oxygen only, RR 0.80 (99% CI 0.67−0.96); invasive mechanical
ventilation, RR 0.65 (99% CI 0.48−0.88).
Dexamethasone
better Usual care
better
No oxygen received 85/501 (17.0%) 137/1034 (13.2%) 1.22 (0.93−1.61)
Oxygen only 275/1279 (21.5%) 650/2604 (25.0%) 0.80 (0.70−0.92)
Invasive mechanical ventilation 94/324 (29.0%) 278/683 (40.7%) 0.65 (0.51−0.82)
Trend across three categories: χ1
2=11.49; p<0.001
All participants 454/2104 (21.6%) 1065/4321 (24.6%) p<0.001
0.83 (0.74−0.92)
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 22, 2020. .https://doi.org/10.1101/2020.06.22.20137273doi: medRxiv preprint
