Friday, 14 August 2020

Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report

COVID-19 and the cheap, old, boring drug that could treat it

Beyond supportive care, we currently don’t have much to treat COVID-19. Remdesivir might decrease hospital length of stay. But we have found no medications that save lives.

The unprecedented RECOVERY trial involves 176 NHS organizations in the UK and are answering clinical questions at an lightning pace. This adaptive RCT has been looking at the use of dexamethasone, hydroxychloroquine, lopinovir/rotonavir, tocilizumab, and convalescent plasma.

This “preliminary report” is publishing the data on dexamethasone.

The background is COVID-19 often results in some immune mediated lung injury. Could steroids mitigate this? Or might they may cause harm by inducing immunosuppression?

6425 hospitalized patients with COVID-19 were randomized in a 1:2 fashion to dexamethasone vs. usual care.

The primary outcome was all-cause mortality at 28 days. They had a bunch of prespecified secondary outcomes.

The dose of dexamethasone was 6mg/day for 10 days.

Results?

Mean age was 66. Median days from symptom onset was 8 days. 16% of them were intubated and 60% were getting supplemental oxygen. 24% had no oxygen requirements.

Overall, 23% of patients randomized to dexamethasone died while 25% died in the usual care group for a number needed to treat (NNT) of about 35. (Rate ratio 0.83, 95% CI 0.75-0.93; P less than 0.001)

But it seemed to work the best in the sickest patients. Those who were intubated had an absolute mortality reduction of 12% for an NNT of 8. Those only on supplemental oxygen derived small benefit at a 3% reduction.

Unfortunately, it appears there is a trend toward harm in patient not requiring oxygen with a number needed to kill of about 26.

With the multitude of crap quality studies being rushed to publication, this is an absolute breath of fresh air. Prior to the final manuscript, this study has already changed the guidelines around the world.

Bottom line?

Intubated patients should get dexamethasone. We should probably give it to sicker patients on oxygen, but avoid it in everyone else.

Of course, this could all change tomorrow…

 

Covering:

Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report. NEJM. 2020,  DOI: 10.1056/NEJMoa2021436 [link to full text article]

 

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