
Efficacy of hydroxychloroquine in patients with Covid-19: a randomized trial - jaboutboul
https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2
======
tangue
I live in an island where during a viral outbreak some were advocating for
chloroquine against the Chikungunya virus. The initial in-vitro tests were
promising but it turns out during human trials it has a reverse effect and
delayed adaptive immune responses (1). It's sad to see scientific method
destroyed by politics and social networks.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977261/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977261/)

~~~
Alex3917
> It's sad to see scientific method destroyed by politics and social networks.

If there were such a thing as phase 5 trials with at least a million
participants, it would be completely insane to use anything that had only
undergone phase 3 clinical trials. People should make rational decisions based
on the best evidence that's available at the time. Whether or not it's
rational to take HCQ, there's nothing magical about phase 3 studies.

Antiviral drugs only really work in the first couple days of the illness, and
with this disease you usually don't get symptoms until at least day 5. And in
the current environment, no one is getting put on prescription antivirals
until at least day 10, and usually even later. To me this raises the question
of whether clinical trials are really even possible right now in the first
place, or whether making decisions based off in vitro data is the best we can
do for right now.

~~~
James_Henry
>To me this raises the question of whether clinical trials are really even
possible right now in the first place, or whether making decisions based off
in vitro data is the best we can do for right now.

I don't think I understand this. We have a clinical trial with in vivo data
right here though, right?

~~~
Alex3917
> We have a clinical trial with in vivo data right here though, right?

AFAIK there's no clinical trial data, but there is in vivo data. My point
though is that these are drugs that block viral replication, and we're mostly
only administering them after the virus has already finished replicating. So
in that scenario of course it's going to look ineffective regardless of
whether it actually works or not. I don't believe the data showing it works,
but I also don't believe the data showing it doesn't work.

~~~
James_Henry
When you say clinical trial, what are you meaning? I think the usual
definition would include this paper as a clinical trial. Do you mean the FDA
hasn't overseen any clinical trials?

Also, why don't you believe the data? or is it the conclusions that the
researchers draw from the data that you don't believe? The statistics and
trial design in this paper seem to be sound.

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arcticbull
The sample size is 62 and the mortality rates are between 0% and 7% depending
primarily on age and co-morbidities. I don't think we can draw any meaningful
conclusions from this other than what we already know: seems worth looking
into HCQ more.

~~~
James_Henry
They weren't looking at the effects on mortality. They looked at TTCR ("the
return of body temperature and cough relief, maintained for more than 72 h")
and radiological changes. They found a decently large effect in both of these.

The meaningful conclusion is "Considering that there is no better option at
present, it is a promising practice to apply HCQ to COVID-19 under reasonable
management."

~~~
James_Henry
Also, you don't need to decrease mortality to have a huge benefit from a
treatment. If you just get people recovering faster, you've probably
indirectly saved many lives!

------
blakesterz
I know someone with Lupus, as I'm sure many people do. This is really good
news for most everyone right now. But for people who need these types of drugs
to fight Lupus (and I'd assume many other diseases) this is really bittersweet
because they can either not get it at all now, or only get a very small
amount. It's good to see this is going to help people with Covid-19, I really
hope the drug makers can get this production ramped up fast so others that
need these drugs can get what they need again.

------
wavepruner
"Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and
53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No
difference in the age and sex distribution between the control group and the
HCQ group. But for TTCR, the body temperature recovery time and the cough
remission time were significantly shortened in the HCQ treatment group.
Besides, a larger proportion of patients with improved pneumonia in the HCQ
treatment group (80.6%, 25 of 32) compared with the control group (54.8%, 17
of 32). Notably, all 4 patients progressed to severe illness that occurred in
the control group. However, there were 2 patients with mild adverse reactions
in the HCQ treatment group. Significance: Among patients with COVID-19, the
use of HCQ could significantly shorten TTCR and promote the absorption of
pneumonia."

------
erikstarck
“ Significance: Among patients with COVID-19, the use of HCQ could
significantly shorten TTCR and promote the absorption of pneumonia.”

~~~
Dobbs
So hate to ask this, can you explain this for non-medical spectators?
Specifically what TTCR and is "absorption of pneumonia" a good thing (e.g. the
body has absorbed the pneumonia and therefore it has gone away) or a bad thing
(e.g. the body has absorbed the pneumonia and therefore has "collected" more)?

 _From Paper:

TTCR: Time to clinical recovery_

~~~
wcoenen
I have a feeling that this is a mistranslation, not jargon. Other similar
usage of "absorption" that I can find was also written by Chinese researchers.

 _edit_ : got downvoted, so adding link to only other "absorption of
pneumonia" use that I could find:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344839/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344839/)

 _edit2_ : I could also find some usage of "absorption of inflammation", again
also all Chinese researchers.

------
aazaa
It's worth noting that this study does not include azithromycin in the
treatment regime, as was the case in the Raoult/French study.

The French study, problematic in the extreme but still promising, claims a
large synergistic effect of using both drugs in combination.

Also, unlike the French study, this one appears to be at least controlled, but
possibly not blinded.

~~~
kiloDalton
I think this counts a double blind trial. From the top of page 4 in the
article: "Randomization was performed through a computer-generated list
stratified by site. Treatments were assigned after confirming the correctness
of the admission criteria. Neither the research performers nor the patients
were aware of the treatment assignments."

------
davidw
Seems relevant:
[https://twitter.com/SquawkCNBC/status/1245669685267439616](https://twitter.com/SquawkCNBC/status/1245669685267439616)

Not sure they've been doing proper studies and such because they're so
slammed, but it seems they've been trying it in Italy and... maybe it helps
some, but doesn't seem like it works miracles.

~~~
Recurecur
In combination with antibiotics and (it seems) zinc it looks quite effective.

A doctor in NY has treated with that combination and is up to almost 700
COVID-19 patients without one dying _or needing a ventilator_.

Some relevant quotes:

>Dr. Zelenko said the whole treatment costs only $20 over a period of 5 days
with 100% success. He defines success as “Not to die.” Dr. Zelenko first
posted his Facebook video message last week calling on President Trump to
“advise the country that they should be taking this medication.”

>There are many other success stories about hydroxychloroquine across the
country. Last week, Dr. William Grace, an oncologist at Lenox Hill Hospital in
New York City, said they’ve not had a single death in their hospital because
of hydroxychloroquine. “Thanks to hydroxychloroquine, we have not had a death
in our hospital,’ Dr. Grace said.

From:

[https://techstartups.com/2020/03/28/dr-vladimir-zelenko-
now-...](https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-
treated-699-coronavirus-patients-100-success-using-hydroxychloroquine-sulfate-
zinc-z-pak-update/)

When people are dying in large numbers, sometimes "anecdotal evidence"
(especially with large samples) is plenty.

~~~
scribu
Edit: Thanks for linking to the source

Snopes has more details of side-effects etc: [https://www.snopes.com/fact-
check/zelenko-669-coronavirus-pa...](https://www.snopes.com/fact-
check/zelenko-669-coronavirus-patients/)

~~~
jdhn
Snopes has it marked as unproven, so it just means that they're waiting for
more results to come in.

For anybody who's interested, here's an interview with the doctor himself:
[https://forward.com/news/national/442285/coronavirus-
hydroxy...](https://forward.com/news/national/442285/coronavirus-
hydroxychloroquine-trump-doctor/)

------
zimpenfish
View from a pharma-focused organic chemist:

[https://blogs.sciencemag.org/pipeline/archives/2020/03/31/co...](https://blogs.sciencemag.org/pipeline/archives/2020/03/31/comparing-
chloroquine-trials)

TL;DR: better than the French paper but that's a low, low bar

------
Gimpei
Sample size seems small. Is this adequately powered given the effect size?

~~~
bart_spoon
Power wouldn't be a concern here. Power is simply the probability that, if a
statistically significant difference exists, the study correctly conclude
there is a difference. Essentially, if a study comes back failing to reject
the null hypothesis ("there is no benefit to hydroxychloroquine"), then you
might be concerned about power ("perhaps there is a benefit and our sample
size was too small to detect it"). There may be other statistical points to be
raised about the results of this study, but given that the null was rejected
("there was evidence of an effect of HCQ"), power wouldn't be among them.

Here the null hypothesis is that hydroxychloroquine isn't any better than not
receiving anything. If the study

------
coding123
So it works?

~~~
arcticbull
Too small a sample size to say.

~~~
James_Henry
Could you show me the statistics/theory that show that this is too small a
sample size to make meaningful decisions from?

~~~
arcticbull
Statistical significance:
[https://en.wikipedia.org/wiki/Statistical_significance](https://en.wikipedia.org/wiki/Statistical_significance)

~~~
James_Henry
So, are you trying to say that the results that the researchers say are
statistically significant aren't actually statistically significant? They give
their numbers in the paper and the p-values are less than everyone's favorite
threshold (.05).

If you are trying to say that their sample size was too small to find an
effect using null hypothesis testing, then that makes no sense.

------
D13Fd
I wish the current U.S. administration hadn't tried to turn this into a
partisan issue.

~~~
Recurecur
It absolutely did not.

The press did.

The mainstream US media has become a one-sided partisan cheerleading squad for
the Democrats, and most Americans are sick of it. We'll see how that works out
in November.

~~~
philjohn
Let's not jump the gun yet - not even been peer-reviewed.

~~~
bart_spoon
I would argue that its being peer-reviewed as we speak. The typical peer-
review process involves having other experts review the paper, for free,
before publication. One small silver lining of this pandemic is the urgency
has caused the scientific model to shift towards preprints, which are rapidly
disseminated among the scientific community via places like Twitter and
Reddit, and notable papers end up getting vetted by many, many more experts
much more quickly than they would via the traditional process. I've already
seen many flawed papers quickly debunked and shot down, and others quickly
floated to the top of the discussion, via experts commenting on Twitter and
elsewhere.

I wonder if after all this is over, if our methods of modern science are
changed forever, or if we just revert to where we were before.

------
karl11
Based on this and all the other anecdotal studies plus all the people treated
with it for other ailments, it seems fairly certain that at a minimum this
treatment is not causing more harm. Given that plus all the indications that
it seems to help to some degree, we should be pursuing production scale of
these drugs aggressively.

It is very unfortunate that the media politicized this treatment in such a way
that now everyone who dislikes Trump carries an initial bias against it.

~~~
orwin
I'm not american and i really, really don't care about trump now (i did in
2017 when i wanted an internship in Ohio that was denied cause new policies
and all that stuff but i eventually found something better, so i'm not angry
about it).

Antiviral drugs will always be given to late in this disease case, maybe it
can reduce infectuosity but we don't know enough yet.

Maybe giving it to everyone to prevent the disease before its even there could
be helpfull, but if i had to take HCQ, i will have to stop taking my
antihistamine drugs, and going into april/may, this is a big no for me.

The fact that it can also reduce the autoimmune reaction is really interesting
though, so maybe giving it to mild cases will prevent them to destroy their
own cells, but this is also dangerous as the disease can cause myocard lesions
(probably the autoimmune reaction, but we don't know yet).

In any case, talking about it is useless before more data arrive: even if we
could give HCQ to everybody, the lockdown is still necessary until the first
wave decrease (at least in France). Don't forge an opinion on something this
early, it will be hard to let it go if you're wrong, and being right early
don't give you anything.

