Thread by @leticiakawano

1/ It's out! The Codex trial.
This is the 2nd RCT result published as a result of an unprecedented collaborative research effort, the Coalition Covid19 Brazil 🇧🇷.
Deserve special recognition: @azevedo_lcp @ICURevisited and all HSL team!

jamanetwork.com/journals/jama/… @JAMA_current

2/ In the Codex trial, mod-severe Covid-19 ARDS cases were randomized to Dexa 20mg/d for 5 days followed by 10mg/d for more 5 days.

*Dexa increased the number of days alive & free of mechanical ventilation in 28 days*

PS: for MV-free days, death was penalized as 0 free days

3/ When you breakdown the composite 1ary outcome in its components, note that mortality was the major driver of difference between groups. No short-term difference in AE was noted:

4/ Look at the characteristics of the pop that benefited from Dexa. Codex included mostly severe pts (high control group mortality rate!)

Note this was a pop of challenging MV:
Pao2/Fio2 ~130; PEEP 11; TV ˜6ml/kg but still MV ~9.5! Huge resp drive (pointing to ⬆️ dz severity)

5/ Steroids were used in 9% of cases of the control group (for other indications). Note that this would bias the results towards the null.
Subgroup analyses don't show any interaction w disease severity (in the MV pt), bottom line:

6/ Together w Codex, in this issue of @JAMA_current, 2 other RCTs* and a WHO MA were published on the topic.
*REMAP-CAP trial
*CAPE-Covid

The association between steroids and reduced mortality was similar for dexamethasone and hydrocortisone, suggesting...

7/ the benefit of steroids seems 2 b a general class effect (not specific to any particular steroid)
About dosing:
lower- vs higher-dose
regimens seems to have similar efficacy, but there's still some imprecision around it so the question of dose is less definitively answered;

8/ For a nice reflection on the issue of steroids for Covid19, I refer you to @HalliePrescott and @toddrice_ICU excellent editorial: jamanetwork.com/journals/jama/…

(This is science fighting Covid19)
#StandUpForScience