
First hydroxychloroquine randomized controlled trial: results disappointing - aaavl2821
https://twitter.com/gcbioinv/status/1242268829906018304
======
throwaway5466
For people that didn't read: it's "disappointing" because both the control and
study groups largely tested negative (93% and 87% respectively). That 87%
figure sounds worse than the control but it actually is better than in the
French study.

What happened in essence is that almost all cases were mild so the patients
almost all got better after a while, with or without medication. This doesn't
mean HCQ is ineffective, only that its efficacy couldn't be measured in this
instance. And I wouldn't call a study where almost everyone gets better at the
end "disappointing".

~~~
cycrutchfield
It's disappointing because it's no better than placebo.

~~~
arcticbull
In this case (as with many others) placebo is pretty effective, but also,
these folks didn't get sick enough to need it, as with the overwhelming
majority of young and healthy people. Another, broader study is required. I'm
sure we'll find out more soon -- this reads like a mulligan though.

~~~
dajohnson89
any data on what percentage of “young healthy” people die/get hospitalized?
also, what’s the definition of young and healthy?

~~~
Terretta
_Across the United States, 38 percent of those hospitalized were between the
ages of 20 and 54._

 _Nationally, 12 percent of the intensive care patients were between the ages
of 20 and 44._

[https://www.nytimes.com/2020/03/23/nyregion/nyc-
coronavirus-...](https://www.nytimes.com/2020/03/23/nyregion/nyc-coronavirus-
young.html)

~~~
bmm6o
I keep hearing statistics like this and I yell at my TV every time. Counting
up the people in the hospital is pretty easy, but it doesn't answer the more
important question of how many infected 20-54 require hospitalization. Even
comparing those numbers to the larger demographics would be helpful.

~~~
Terretta
There are a variety of these sources.

[https://statmodeling.stat.columbia.edu/2020/03/07/coronaviru...](https://statmodeling.stat.columbia.edu/2020/03/07/coronavirus-
age-specific-fatality-ratio-estimated-using-stan/)

[https://www.statista.com/chart/21173/hospitalization-icu-
adm...](https://www.statista.com/chart/21173/hospitalization-icu-admission-
and-fatality-rates-for-reported-coronavirus-cases/)

------
hampelm
Why are we amplifying someone posting a compressed jpeg to 3,000 followers who
lists no name, has a photo of George Costanza, and claims to be a virologist?

~~~
bdcravens
Perhaps they are infinitely more qualified than some of the public figures
pushing this treatment as a "game-changer"? Either way, hopefully we'll hear
from some well-identified, qualified experts in time.

------
djvu9
It is a 30 patients test and almost everybody’s fever was gone right after
enrollment. Even the swab test results turned negative in 2-4 days. Why is
medicine ever needed for such group of patients?

~~~
jansan
The results are disappointing because they are useless. That's how I interpret
the headline.

------
nikolay
I am sorry, but isn't the mechanism of action that hydroxychloroquine is
simply a zinc ionophore, i.e. you need enough free zinc in the blood for this
to work? I read doctors suggesting using hydroxychloroquine along with 50mg of
ionic zinc.

~~~
omgwtfbyobbq
Like Reelin said, it's effectiveness may be related to it's ability to
modulate immune activity by affecting pH.

[https://www.ncbi.nlm.nih.gov/pubmed/27927040](https://www.ncbi.nlm.nih.gov/pubmed/27927040)

Course, that'll only work if the symptoms are being caused by an overactive
immune system and it's able to mediate that immune response in time.

~~~
arcticbull
> Course, that'll only work if the symptoms are being caused by an overactive
> immune system and it's able to mediate that immune response in time.

Accumulating evidence suggests that a subgroup of patients with severe
COVID-19 might have a cytokine storm syndrome [1]. HCQ is known to moderate
this reaction.

[1]
[https://www.thelancet.com/journals/lancet/article/PIIS0140-6...](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736\(20\)30628-0/fulltext)

~~~
omgwtfbyobbq
I'm not sure if it would be able to mitigate a cytokine storm, but it could
prevent it. When DW was on it for sepsis due to an auto-inflammatory
condition, her progression was much slower than what I've read about cytokine
storm.

~~~
arcticbull
Thanks, I misspoke.

------
hannob
Has anyone found the study they're talking about? This tweet is only a
screenshot of the abstract.

And the trials registry entry says "No results published":
[https://clinicaltrials.gov/ct2/show/NCT04261517](https://clinicaltrials.gov/ct2/show/NCT04261517)

Update: I asked the person on twitter and here it is:
[http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43...](http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf)
Apparently it's in chinese.

~~~
ankushnarula
Yes. Two issues...

Median age for the control group and test group was 24yrs and 18yrs
respectively. This isn't the ideal sample group for testing this drug for
COVID-19 indication.

But more importantly... Dosing was only 400mg once per day versus recommended
500mg twice per day as performed in the French trial.

Taken together, this trial tells us very little on how this drug would perform
at proper dosing on severe subjects in vulnerable age range and/or with prior
co-morbidities.

------
aaavl2821
didnt find a link to the abstract, seems the results are just being published

link to the trial on clinicaltrials.gov is here:
[https://clinicaltrials.gov/ct2/show/NCT04261517](https://clinicaltrials.gov/ct2/show/NCT04261517)

patients in both tx and control arm fared better than in the french study from
earlier this week, suggesting patients were healthier / lower risk at baseline

patients got slightly lower dose in this study (400 mg / day) vs the french
study (600 mg / day)

~~~
raphlinus
Someone on the Twitter thread linked to this, which seems to be not exactly
the same document but contains very similar text in the abstract:

[http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43...](http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf)

I think it helps if you can read Chinese, though Google Translate seems to do
a pretty ok job on it.

~~~
HarryHirsch
No need to read Chinese, the abstract is on page 2. Conclusion: at current
trial size no better than placebo. More study is needed to tease out an
effect, if there is any.

~~~
rurban
It does help if you read the translation.

By now everybody should know that the successful dosis is 2x500mg per day for
10 days. Not 1x 400mg per day, which is the old dosis for Malaria prevention.
This dosis needs at least 2-3 weeks to be effective (saturate the cell
membranes with zinc), and by then the infection is already over. And the
Chinese treatment plan contained much more.

A study with zero value.

~~~
newsbinator
What's the source of this?

~~~
rurban
The official chinese treatment recommendation.
[https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_ar...](https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_article_from_the_shanghai_medical/)

Amongst doctors both hydroxychloroquine sulfate and chloroquine phosphate run
under broadband antiviral.

------
sanxiyn
Here is actual publication:
[http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2...](http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03)

------
JohnJamesRambo
> That was a first run trial without the Zpak. The following trial with both
> showed 100% efficacy after 5-6 days.

Is that twitter reply accurate?

~~~
sfteus
No, that trial has some glaring flaws. Several threads go into them way better
than I could.

[https://twitter.com/GaetanBurgio/status/1241201751916568576](https://twitter.com/GaetanBurgio/status/1241201751916568576)

[https://twitter.com/MicrobiomDigest/status/12414295448478638...](https://twitter.com/MicrobiomDigest/status/1241429544847863808)

~~~
JohnJamesRambo
Thank you for the links! I didn’t know about those gremlins in the
supplementary info. Hopefully the WHO trials recently announced will give us a
better answer soon.

------
known
In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical
researchers stated that exploratory research into chloroquine and two other
medications, remdesivir and lopinavir/ritonavir, seemed to have "fairly good
inhibitory effects" on the SARS-CoV-2 virus, which is the virus that causes
COVID-19. Requests to start clinical testing were submitted.[43] Chloroquine
had been also proposed as a treatment for SARS, with in vitro tests inhibiting
the SARS-CoV virus.[44][45] However, at least one case of self-medication with
chloroquine for COVID-19 has caused a fatality, and the Nigeria Centre for
Disease Control has stated that such self-medication "will cause harm and can
lead to death."

Chloroquine has been recommended by Chinese, South Korean and Italian health
authorities for the treatment of COVID-19.[47][48] These agencies noted
contraindications for people with heart disease or diabetes.[49] Both
chloroquine and hydroxychloroquine were shown to inhibit SARS-CoV-2 in vitro,
but a further study concluded that hydroxychloroquine was more potent than
chloroquine, with a more tolerable safety profile.[50] Preliminary results
from a trial suggested that chloroquine is effective and safe in COVID-19
pneumonia, "improving lung imaging findings, promoting a virus-negative
conversion, and shortening the disease course."[51] Self-medication with
chloroquine has caused one known fatality.

[https://en.wikipedia.org/wiki/Chloroquine#COVID-19](https://en.wikipedia.org/wiki/Chloroquine#COVID-19)

------
cycrutchfield
Thank goodness that we are actually getting some RCT results. There has been a
huge confirmation bias towards any positive results for chloroquine, no matter
how specious or flawed the underlying science was. Everybody wants this to
work because the drug is well-tested on humans, cheap, and broadly available.
It would be a panacea, a miracle drug. My concern is that the desire for this
drug to be effective has clouded people's judgment (even seasoned researchers)
and led to bad science.

~~~
whatshisface
> _It would be a panacea, a miracle drug._

Not really, a panacea is a drug that cures everything. If chloroquine was
found to be an effective antiviral, it would only be a drug that cured _two_
things. That's common enough to not warrant excessive skepticism taken alone.

~~~
TheAdamAndChe
While that may be the precise definition of a panacea, the vernacular
definition is a breakthrough or unexpected good thing.

------
fourcolordeck
It's two samples of 15. 13/15 and 14/15 successes. Much too small to draw any
conclusions. It's even noted a larger sample size is needed

------
mirimir
Wait. I thought that hydroxychloroquine was hypothesized to protect against
wet lung, as an anti-inflammatory, and not as an antiviral.

Did I just make that up?

~~~
rurban
No, HCQ is the Antiviral. Anti-inflammatories are also in the plan, but not
Iboprofen.

~~~
arcticbull
Not exactly. HCQ has anti-inflammatory action as well as immune moderating
action [1] the latter of which may help protect against cytokine storm which
occurs in some serious COVID-19 infections. It also has antiviral action in
some situations but it's not clear that that's actually relevant to COVID-19
yet.

[1]
[https://en.wikipedia.org/wiki/Hydroxychloroquine](https://en.wikipedia.org/wiki/Hydroxychloroquine)

~~~
mirimir
Thanks. Upon reflecting, I meant to say immune moderating as well as anti-
inflammatory. Which is why it's become so popular for treating arthritis.

I wonder about the antiviral activity, though. What I've read is about
possibly faster drop in virus levels. And I suppose that HCQ could be
interfering with some stage of intracellular virus production. But time will
tell.

~~~
rurban
You're mixing it up: CQ Phosphat is the rheuma/arthritis treatment, HCQ Sulfat
the malaria prevention drug. CQ has much more severe side-effects, esp. in
blacks. HCQ can lead to temporal blindness after years of use. We are talking
10 days here.

------
HarryHirsch
Not unexpected. A week or two ago a Chinese treatment protocol made the rounds
where hydroxychloroquine was suggested as an alternative to HIV protease
inhibitors. Since we now know that ritonavir/lopinavir doesn't work well, one
wouldn't expect hydroxychloroquine to do any better. If it had remarkable
clinical effects _it_ would be the first-line treatment.

------
roenxi
This is evidence; it isn't great but it also isn't conclusive. We'll need to
wait longer for something a little more decisive. A twitter link is also
unhelpful because we only get a blurry abstract to go off.

The happy dream is maybe hydroxychloroquine has prophylactic tendencies since
it is something people can take long term to be at a substantially lower risk
vs catching COVID. The abstract doesn't really show much either way on that
front.

Spitballing as an amateur, I suspect once someone has actual symptoms or is
verging on a serious case it is too late to help - what is a drug supposed to
do, regrow a busted lung? It comes to a point where the virus isn't what is
killing you, it is the damage the virus did while breeding and/or the immune
system overreacting fighting back and going haywire. Antivirals should help
but aren't expected to be magic for either of those things.

~~~
antonvs
> The happy dream is maybe hydroxychloroquine has prophylactic tendencies
> since it is something people can take long term to be at a substantially
> lower risk vs catching COVID.

It's an immune system inhibitor, so this seems like a bad plan.

~~~
rdtsc
> It's an immune system inhibitor, so this seems like a bad plan.

Not unless the cytokine storm is what ends up killing the patient in the end.

[https://www.vox.com/2020/3/12/21176783/coronavirus-
covid-19-...](https://www.vox.com/2020/3/12/21176783/coronavirus-
covid-19-deaths-china-treatment-cytokine-storm-syndrome)

Then it may be a good idea. The immune system is a very complex _system_ so
some parts may be active and some parts suppressed at the same time and that
may be what’s need for the fastest recovery.

------
microcolonel
It seems like the study was conducted on the complete wrong set of patients.

------
akarve
The reported dosage is less than half what the Chinese Government recommends
(500mg x 2 (BID)). So it's possible that they didn't hit the effective dose.
[https://medium.com/@balajis/the-official-chinese-
government-...](https://medium.com/@balajis/the-official-chinese-government-
guide-to-diagnosing-and-treating-the-novel-coronavirus-9d06868f8df4)

~~~
hcknwscommenter
your link is to chloroquine phosphate, which has a phosphate group and is only
like 75% chloroquine by weight. So no, not less than half. Moreover, you are
trying to compare a hydroxychloroquine dose with a chloroquine phosphate dose
(active ingredient is chloroquine, not hydroxychloroquine), which is any one's
guess if they even have the same mechanism of action here. Just because they
both work against malaria, doesn't mean much about this virus. All in all, it
is nearly useless to compare the chloroquine phosphate dose and outcomes to
the hydroxychloroquine dose and outcomes.

