Major Covid treatment breakthrough? - Dexamethasone

[George K]

Decadron Dexamethasone is a steroid - not really different from prednisone, cortisone or others, except in terms of potency (when I used to give it, it was on the order of 4-12 mg, vs. 100 mg or more of cortisone).

It's perhaps a better anti-inflammatory than other steroids, but, it is just a steroid.

A 20-30% reduction in mortality is a big deal, to be sure, but it's not something that actually takes care of the virus. Rather, it treats the effects of the virus.

[George K]

Science by Press Release:

https://respectfulinsolence.com/2020/06/17/dexamethasone-and-hydrochloroquine-a-tale-of-two-drugs-for-covid-19/

Speaking of the Recovery Trial, the one thing about its finding that hydroxychloroquine has no activity against COVID-19 in patients hospitalized with COVID-19 that bothered me two weeks ago, when it was first announced, is that there was no manuscript, no peer-reviewed paper. It was science by press release. There was also a difference. While the supposed finding that hydroxychloroquine showed no benefit in hospitalized patients with COVID-19 was reported almost as an afterthought, the press release from the Recovery Trial reported yesterday was breathlessly reported as “new hope” for COVID-19 by basically every news outlet I recall seeing, with hardly a word of skepticism or caution, with the BBC news being all in, complete with the headline Coronavirus: Dexamethasone proves first life-saving drug, spun thusly:

A cheap and widely available drug can help save the lives of patients seriously ill with coronavirus.

The low-dose steroid treatment dexamethasone is a major breakthrough in the fight against the deadly virus, UK experts say.

The drug is part of the world’s biggest trial testing existing treatments to see if they also work for coronavirus.

It cut the risk of death by a third for patients on ventilators. For those on oxygen, it cut deaths by a fifth.

Had the drug had been used to treat patients in the UK from the start of the pandemic, up to 5,000 lives could have been saved, researchers say.

And it could be of huge benefit in poorer countries with high numbers of Covid-19 patients.

The UK government has 200,000 courses of the drug in its stockpile and says the NHS will make dexamethasone available to patients.

Prime Minister Boris Johnson said there was a genuine case to celebrate “a remarkable British scientific achievement”, adding: “We have taken steps to ensure we have enough supplies, even in the event of a second peak.

Notice that last paragraph? This finding is being presented in nationalistic terms, as a great triumph of British science, a gift from Britain to the world. All of this, before there’s even a peer-reviewed scientific paper describing what was actually found. Instead, all we have is science by press release.

I can’t help but quote this particularly apt Tweet:

Just reflecting on the fact that today, doctors all around the world changed how we treat COVID-19 based upon a study we haven't even been able to read yet.

— David Juurlink (@DavidJuurlink) June 16, 2020
And this one:

It will be great news if dexamethasone, a cheap steroid, really does cut deaths by 1/3 in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper. https://t.co/ZP5GVMUCW3

— Atul Gawande (@Atul_Gawande) June 16, 2020
Personally, I can’t help but note that the question of whether steroids like dexamethasone improve survival in ARDS (regardless of the cause, including COVID-19), regardless of the cause, is not a new question. ICU docs were debating the question in the late 1980s, when I started by surgery internship, continued debating it the entire time that I was doing my surgery residency in the early 1990s, and are still debating it today. Indeed, in my own current department there was recently a talk discussing the management of ARDS that mentioned when and how to introduce steroids. You’d think that after decades of controversy, with literally dozens of randomized trials of steroids in severe ARDS, we’d have an answer, but we really don’t. Personally, I like this observation:

Steroid reduces mortality in some studies, but not others. This is a topic of perpetual, internecine struggle which will probably never be resolved.
And this one:

At this point, there is a fair body of evidence that patients with severe pneumonia or septic shock may benefit from steroid (in the absence of contraindications). Whether mortality benefit occurs is contentious, but it does seem that steroid accelerates ventilator weaning and ICU discharge (which are meaningful, patient-centered outcomes). So steroid makes sense for patients with {pneumonia+ARDS} or {sepsis+ARDS}. That isn’t a change in my practice.

The real question is whether patients with ARDS who don’t have pneumonia or sepsis should be treated with steroid. This remains murky. Patients may need to be judged on a case-by-case basis (depending on whether the suspected cause of ARDS is thought to be a steroid-responsive process). In the absence of any clear-cut answer, one possible approach is to use CRP as a signal for patients with systemic inflammation who might benefit from steroid. There is some precedent for this in the literature, as one RCT of pneumonia used CRP as a cutoff to adjudicate whether steroid would be used.​11​
In other words, in severe inflammatory diseases of the lungs, it was unclear whether dexamethasone or other steroids are of benefit. That’s why I really, really, really want to see the actual data. That’s why I agree with Atul Gawande:

[taiwan_girl]

@George-K said in Major Covid treatment breakthrough? - Dexamethasone:

A 20-30% reduction in mortality is a big deal, to be sure, but it's not something that actually takes care of the virus. Rather, it treats the effects of the virus.

I think this is a good point. It is great if it works, but it it after the fact. We need something for before the fact.

[Doctor Phibes]

@George-K said in Major Covid treatment breakthrough? - Dexamethasone:

Notice that last paragraph? This finding is being presented in nationalistic terms, as a great triumph of British science, a gift from Britain to the world.

Donald did say that Boris was British Trump. Of course, we Brits knew all along that Donald was an American Johnson.

[Aqua Letifer]

@Doctor-Phibes said in Major Covid treatment breakthrough? - Dexamethasone:

Donald was an American Johnson.

Nice.

[Axtremus]

https://www.nytimes.com/2020/06/24/health/coronavirus-dexamethasone.html

Breakthrough Drug for Covid-19 May Be Risky for Mild Cases
‘That study about dexamethasone has arrived with a big asterisk: While it appears to help severely ill patients, it harms others.’

[Loki]

@Axtremus said in Major Covid treatment breakthrough? - Dexamethasone:

https://www.nytimes.com/2020/06/24/health/coronavirus-dexamethasone.html

Breakthrough Drug for Covid-19 May Be Risky for Mild Cases
‘That study about dexamethasone has arrived with a big asterisk: While it appears to help severely ill patients, it harms others.’

Who is this for? The public not to take it without doc’s consent. The risk factors for it are very well known.

[George K]

Decadron (dexamethasone) is a potent steroid - about 20 times more potent than hydrocortisone, iirc.

Its primary effect is anti-inflammatory.

Steroids are known to increase the risk of infection, so...

And this:

Dexamethasone was beneficial for those who had been sick for more than a week, reducing deaths by one-third among patients on mechanical ventilators and by one-fifth among patients receiving supplemental oxygen by other means.

Patients given the steroid who were not receiving respiratory support, however, actually died at a slightly higher rate than similar patients who were not given the drug, although the difference was not statistically significant.

[LuFins Dad]

I’m all in on Famotodine!
https://www.medrxiv.org/content/10.1101/2020.05.01.20086694v2

[George K]

Anti-inflammatory:
Dexamethasone hailed as lifesaver for up to a million Covid patients worldwide

Dexamethasone – the inexpensive steroid that quickly emerged as a highly effective Covid therapy thanks to a large drug testing programme pioneered by UK scientists – has so far saved the lives of an estimated million people globally, including 22,000 in the UK, according to NHS England.

Called Recovery, the world’s largest randomised Covid-19 drug trial commenced in March 2020 to evaluate the suitability of a suite of different drugs to help hospitalised Covid patients. The study has since been carried out by thousands of doctors and nurses on tens of thousands of patients in hospitals across Britain.

As Covid-19 emerged in late 2019, Oxford University’s Peter Horby, an infectious disease specialist, had begun working on Covid drug trials in Wuhan. But studies were shelved as fierce lockdown restrictions dried up infections in China. Meanwhile, cases began to pop up in Europe.

Horby joined forces with Oxford colleague Martin Landray, a professor of medicine and epidemiology, to set up Recovery. It took them only nine days from drafting their first protocol to the enrolling of the first patient, a process that typically takes nine months.

Less than 100 days after the programme kicked off, trial investigators produced a staggering result – the first medicine that demonstrably improved Covid-19 survival chances. Dexamethasone, a widely available and affordable generic steroid, was shown to cut the risk of death by a third for Covid patients on ventilators, and by nearly a fifth for those on oxygen therapy.

[Rainman]

There was another one called ivermectin as I recall, that was touted as being a great supplement for Covid patients.

Seems I recall the media blasting anything that Trump would say, even if it were a helpful medication.

[Jolly]

@george-k said in Major Covid treatment breakthrough? - Dexamethasone:

Anti-inflammatory:
Dexamethasone hailed as lifesaver for up to a million Covid patients worldwide

Dexamethasone – the inexpensive steroid that quickly emerged as a highly effective Covid therapy thanks to a large drug testing programme pioneered by UK scientists – has so far saved the lives of an estimated million people globally, including 22,000 in the UK, according to NHS England.

Called Recovery, the world’s largest randomised Covid-19 drug trial commenced in March 2020 to evaluate the suitability of a suite of different drugs to help hospitalised Covid patients. The study has since been carried out by thousands of doctors and nurses on tens of thousands of patients in hospitals across Britain.

As Covid-19 emerged in late 2019, Oxford University’s Peter Horby, an infectious disease specialist, had begun working on Covid drug trials in Wuhan. But studies were shelved as fierce lockdown restrictions dried up infections in China. Meanwhile, cases began to pop up in Europe.

Horby joined forces with Oxford colleague Martin Landray, a professor of medicine and epidemiology, to set up Recovery. It took them only nine days from drafting their first protocol to the enrolling of the first patient, a process that typically takes nine months.

Less than 100 days after the programme kicked off, trial investigators produced a staggering result – the first medicine that demonstrably improved Covid-19 survival chances. Dexamethasone, a widely available and affordable generic steroid, was shown to cut the risk of death by a third for Covid patients on ventilators, and by nearly a fifth for those on oxygen therapy.

My FP guy's standard cocktail upon presentation was prednisone (I think 20mgx5days), z-pack, Pepcid, Vitamin D and Vitamin C. the wife was also offered BAM. She should have taken it, but didn't.

[Jolly]

@rainman said in Major Covid treatment breakthrough? - Dexamethasone:

There was another one called ivermectin as I recall, that was touted as being a great supplement for Covid patients.

Seems I recall the media blasting anything that Trump would say, even if it were a helpful medication.

There were docs in Baton Rouge routinely prescribing it. Also some prescribing Plaquenil.

[George K]

@jolly said in Major Covid treatment breakthrough? - Dexamethasone:

Plaquenil

[Jolly]

Yep.

Docs tend to use what they think will work, even if it's only a slim chance. Slim beats none...