Reference: Villar. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 2020; 8: 267–76.
I know what you are thinking, “What gives? No COVID!” Well the two of you who read this are probably inundated with COVID info. So to give our brains a change I thought I would do a study that would DEFINITELY BE A HEADLINE if we weren’t COVID CRA. But just as DC gets overshadowed by Marvel so to this good (but slightly methodologically flawed) study may go unnoticed.
This study look at the utility of dexamethasone (dex) to treat MODERATE to SEVERE ARDS. I say this in bold because other trials didn’t have an entry criteria of a PaO2/FiO2 (“P/F” Ratio) of <200 (usually its worse like <150)…but this one did. Boy did they find a difference. The primary outcome was ventilator free days and they found that dex ALMOST halved this (7.5 vs 12.3)! Secondary outcomes (sloooowwww down those are hypothesis generating…quiet you, I want to be happy about something): All-cause mortality…halved!: (29 vs 50); ICU Mortality halved! (26 vs 43). Well not quite but pretty close. Now before we celebrate like its the end of social distancing* there are a TWO MAJOR FLAWS in the armor of this trial.
Flaw #1. Not only was it open label (the docs knew they were giving a steroid) but there WASN’T a placebo…what the what!!!! They state as follows:
“According to the ethical principles for medical research of the Declaration of Helsinki,19 the use of no placebo (no intervention) is acceptable when no proven intervention exists and when the patients who receive a placebo could be subjected to additional risks (eg, intravenous catheter-associated infections and interaction with other medications). The Spanish Agency of Drugs and Medical Devices and the referral Ethics Committee did not mandate a blinded design nor the administration of a placebo.”
“Although dexamethasone was not administered in a masked manner, the risk of assessment bias is very low because one of the outcomes of interest (mortality) is objective.”
Any who has ever been a patient or spent time as learner (and we are all learners) knows NOTHING is OBJECTIVE. The decision to take someone off the vent earlier COULD absolutely have been influenced.
Flaw #2: The trial was stopped short. The trial was calculated to have 317 parties with 157 in each arm but only ended up with 139 (+1) in each.
The trial was stopped at 88% enrollment due to low enrollment. Stopping a trial short can OVERESTIMATE the effect size.
A minor flaw in this study is that they also took less sick patients than other trials. As is the mantra with research “If it didn’t work, you didn’t give it early enough”…once again this was “right”.
Two good things they did correctly is look at new infections and hyperglycemia in both groups and found no difference.
That being said there looks like a signal here. Im sure when it comes down to it the GIANT changes seen here, they won’t pan out to be as big in real life but I bet there is something to giving dex to ARDS…at least I can hope. As an ER/ICU doc its another reason for me to give steroids… and you can’t spell stERoids without ER!
*I REALLY don’t like the term social distancing/isolation…we should call it “physical distancing/isolation”. We can stay in touch, without the touching!