Narrative Summary Review of Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Narrative Summary Review of Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report
In the New England Journal of Medicine
Published on
July 17, 2020
Research study by P. Horby and Colleagues

In the article Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report published, July 17, 2020, by Horby and Colleagues, from the RECOVERY Collaborative Group, United Kingdom, a Randomized controlled trial, open-label/non-blinded, investigating the question does dexamethasone at 6 mg daily for up to 10 days make a difference in 28-day mortality compared to usual care alone? 

6425 patients were randomized, individuals were included on the basis of hospitalization with clinically suspected SARSCOV2, or laboratory-confirmed SARSCOV2. Pregnant or breast-feeding women were eligible. Excluded patients were those who definitely indicated or definitely contraindicated for dexamethasone therapy (no medical condition may put patients at substantial risk due to trial participation) and those patients at hospitals that had no more dexamethasone were also excluded. Patients in the sample were from 176 National Health Service organizations in the United Kingdom. The study randomized and enrolled patients on March 19, 2020 to June 8, 2020, and is Ongoing; Part of ongoing RECOVERY Collaborative Group research, United Kingdom.

Results were measured by primary outcome/end point= all-cause mortality within 28 days after randomization; and at 6 months. Secondary outcome= time until discharge from hospital, and decision to mechanically ventilate, or death. Other outcomes were followed too. A single online follow-up form was to be completed when the patients were discharged or had died or at 28 days after randomization, which-ever occurred first.

Outcomes of the study revealed 28-Day mortality rates for mechanically ventilated patients in the intervention/dexamethasone group versus usual care group, indicated mortality reduction in the dexamehasone group (29.3% vs. 41.4%; rate ratio, 0.64; 95% Confidence Interval, 0.51 to 0.81). 28-Day mortality rates for non-intubated oxygen supplemented patients in the intervention/dexamethasone group versus usual care group indicated mortality reduction in the dexamethasone group (23.3% vs. 26.2%; rate ratio, 0.82; 95% Confidence Interval, 0.72 to 0.94). 28-Day mortality rates for patients without any respiratory support indicated no significant difference between the interventional/dexamethasone group versus the usual care group, albeit a quanitative signal showed non statistical mortality rate increase in the intervention/dexamethasone group (17.8% vs. 14.0%; rate ratio, 1.19; 95% Confidence Interval, 0.91 to 1.55). Accounting for all patients, the 28 Day mortality events of the Dexamethasone group was lower than that of the Usual care group, 482 of 2104 or 22.9% of the Dexamethasone group, 1110/4321 or 25.7% of the Usual care group, Rate ratio 0.83 Confidence Interval, 0.75 to 0.93, P<0.001.

There were some limitations in the study of which none were explicitly identified by the authors. Firstly, this is a fairly populated study with many moving parts and is even part of a larger study and research collaboration called the RECOVERY Collaborative Group, based in the United Kingdom, via its National Health Service medical facilities. The study is also investigating treatment arms of several other drugs at the same time. There was seconrdary randomization performed for the administration of Tocilizumab in a subset of patients (95 in the intervention/dexamethasone arm and 276 in the usual care arm). Given this, although there is randomization, the the trial design complexity increases several fold, and hampers the ability to have accurate peer-review and analyses given the sheer magnitude of the complexity. The other drugs being studied were not the focus of this preliminary report, but are mentioned in passing and detailed in the supplementary appendix. The age based subgroups are broad for younger ages, ages younger than 70 are all in one group and this may provide less definition and more skew when comparing patients from other subgroups. This is partially but not fully addressed by randomization. The outcomes data indicates statistical 28-Day mortality reduction with dexamethasone however this benefit and difference is not very large and secondary outcome data indicated non-statistical mortality rate reduction. The percentage wise difference is 2.8% greater 28-Day mortality in the Usual care group compared to the Dexamethasone group. Then when compared to the secondary outcome of any death, There is non-statistical mortality reduction, with dexamethasone versus usual care, 21.7% versus 22.7%, a 1% difference with a risk ratio of 0.93 Confidence Interval (0.84 to 1.03).

On an ending note, the authors mentioned that dexamethasone at 6 mg daily for up to 10 days lowers 28 day mortality in COVID-19 patients who are on some form of respiratory support with oxygen. However, it may be harmful in patients not on respiratory support. This reiterates the pharmacological and medicine principle of right drug, right dose, right patient, right time for the right therapy. The United Kingdom medical authorities have adopted glucocorticoids in their guidelines as the United States also adopted it in their National Institutes of Health Guidelines for COVID-19.

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