26 ms·

French researcher posts successful Covid-19 chloroquine drug trial

219 points by jseliger 7y ago

RalfWausE 7y ago
This sounds really promising! I hope this report find its way to the officials...
- raindeer3 7y ago
  Form what I read the UK has already stopped all export of this drug.
  - deleted 7y ago
    [deleted]
  - jaynetics 7y ago
    Yes, alongside Aletra. Source: https://www.pharmaceutical-technology.com/comment/parallel-export-covid-19/ https://www.pharmaceutical-technology.com/comment/parallel-e...
  - 77pt77 7y ago
    This is easy to synthesize and very cheap. It also has potentially irreversible side effects, namely retina damage.
    - stubish 7y ago
      Thankfully retina damage seems to only be from continual use. This is medication people have stayed on for decades. It seems pretty benign for just a few weeks, unlike many medications where the long term side effects can kick in after just months.
aazaa 7y ago
Call me skeptical. The details in this article are insufficient to draw many conclusions. There is no paper, although a YouTube video (in French) is linked. The article doesn't make it clear whether Raoult was being interviewed, or the information was taken from the video. The linked Google Doc (not regarding the study in question, despite another comment on this thread) summarizes results from other purported studies. Even then, this document itself appears to lack the usual signs of authenticity. Be careful about drawing conclusions because the details just aren't there. Details are everything in drug discovery. Edit: Then there's the vague language in the article. > “We were able to ascertain that patients who had not received Plaquenil (the drug containing hydroxychloroquine) were still contagious after six days, but of those that had received Plaquenil, after six days, only 25% were still contagious.” "Contagious" means nothing because AFAIK, there is no test for it. There is a PCR test being used around the world to detect the presence of viral RNA. So it's suspicious that an expert would be using the word "contagious," which implies the ability to transmit the virus under experimental conditions. And it gets worse. Have a look at the video linked in the article: https://www.mediterranee-infection.com/coronavirus-diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/ https://www.mediterranee-infection.com/coronavirus-diagnosti... First, it begins with a title that doesn't match the title of the speaker's slide deck. Second, judging from the slides the video appears to be about COVID-19 testing in general. There doesn't seem to be anything of substance about chloroquine anywhere. I don't speak French, so maybe there is something there. If so, the slide deck doesn't reflect it. And there's no way that a successful clinical trial of a COVID-19 drug would begin with basic introductory slides that everyone already knows. This just doesn't add up. I'm calling bullshit.
- NotAnAccountNO 7y ago
  This is the presentation Raoult gave yesterday, publication is coming next week. https://youtu.be/n4J8kydOvbc https://youtu.be/n4J8kydOvbc Link to the powerpoint. Please don't kill the IHU's servers though: it's all in french. https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20...
  - 7y ago
mrob 7y ago
>Patients were given 600mcg per day for 10 days. Did they really mean micrograms or is this a mistranslation of milligrams? 600mcg is much lower than any dose I've heard of for other conditions.
- ibejoeb 7y ago
  I'm sure it's mg. There is a similar experiment from Melbourne that cites similar dosage. I'll try to find it. Also, it looks like there is a US clinical trial of chloriquine to start in May: https://clinicaltrials.gov/ct2/show/NCT04303507 https://clinicaltrials.gov/ct2/show/NCT04303507
- ComputerGuru 7y ago
  EDIT: this source [0] seems to confirm that it is indeed milligrams, but I don't understand how any of this jives with what I found earlier from the FDA on therapeutic index and overdosing. [0]: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj... See the original comment with my findings from the FDA below, however. --- I don't think it's a mistake. 600mg per day is 14x the recommended dosage for malarial suppression with cholorquine. Per the FDA, the dosage is 300mg of chloroquine per week for malarial suppression: > Adult Dose: 500 mg (=300 mg base) on exactly the same day of each week. For children: > The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight. Source: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/006002s043lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/00... Additionally, it seems that it is incredibly easy to fatally overdose on this: > Chloroquine is very rapidly and completely absorbed after ingestion. Toxic doses of chloroquine can be fatal. As little as 1 g may be fatal in children. Toxic symptoms can occur within minutes. These consist of headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, shock and convulsions followed by sudden and early respiratory and cardiac arrest. Hypokalemia has been observed with arrhythmias in cases of intoxication. The electrocardiogram may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, and progressive bradycardia leading to ventricular fibrillation and/or arrest. Cases of extrapyramidal disorders have also been reported in the context of chloroquine overdose (see WARNINGS and ADVERSE REACTIONS) See also this paper about known cases of overdose in kids: https://pediatrics.aappublications.org/content/27/1/95.long?sso=1&sso_redirect_count=1&nfstatus=401&nftoken=00000000-0000-0000-0000-000000000000&nfstatusdescription=ERROR%3a+No+local+token https://pediatrics.aappublications.org/content/27/1/95.long?... Note that is for all for cholorquine base, not chloroquine phosphate which is ~60% choloroquine.
shanxS 7y ago
From the article Paper: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj... Video(not in English): https://www.mediterranee-infection.com/coronavirus-diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/ https://www.mediterranee-infection.com/coronavirus-diagnosti...
- bertil 7y ago
  That researcher is likely, at best, controversial: - he starts by arguing against quarantine; his point is that it didn’t work for Cholera in 1832; - he dismisses two thirds of the efforts against HIV/AIDS: understanding transmission effort and promoting condoms, focusing on treatment lowering viral load; - he then moves on to framing response to the pandemic in a conspiracy-sounding “shift of power towards the Far East”; - he then says “most countries” have chosen to test extensively early — I don’t think that’s really true: South Korea, has but I don’t think many other did; - he’s surprisingly unmoved by mortality on the cruise boat ashore Japan; I know epidemiologists can seem comfortable with terrifying stats, but he’s more than that. He’s not terrible over all and fairly eloquent to make his case but I’d take his presentation with a grain of salt. Key points: - children don’t seem to be contagious (they are asymptomatic but vectors for the flu); - viral loads are more predictive than anything; - people appear contagious for 20 days; key point isn’t a fix duration but measuring viral load and isolating anyone with a high level; - the hospital has 143 samples, they are looking forward to comparing genes with symptoms. He’s happy that people are attacking him for advertising chloroquinine because the controversy drives traffic… Not sure most doctors would be confortable with that media strategy. He’s unhappy that television features people without qualification, though. He compares his findings with similar findings in China and Korea with slightly different treatment (600 mg vs 2x500 hydroxi-chloroquinine, which he claims to have been the first to propose for other infections). He uses patients from nearby town who didn’t receive the treatment in a quasi-experiment on the impact on viral-load duration. He’s also recommending a combination with an anti-biotic because complications are often microbial. His final point is to not recommend to go home but be tested and treated. I think that he’s onto something scientifically and he could be talking about it on TV but before that, he _needs_ to get some media training to focus on the positive.
fhoe 7y ago
The problem is patients only get this at the point that they require hospitalization. It should be as easy to get a short-term dose of this (unlikely to cause severe side effects) as it is to get a seasonal flu shot, and people should be advised to take it for two weeks (or whatever) at the onset of symptoms, or even as a prophylactic if they know they were exposed.
- fhoe 7y ago
  Instead of being able to order this from Amazon or Walmart online, you have to 1) go to a doctor, NP, or other medical practitioner with prescription power 2) convince them to write you the script (and pay them, directly or indirectly, for this service) 3) have it sent electronically (in NY) to the right pharmacy that can fill it 4) then go to the pharmacy and fill it The rent-seeking in our medical system will be the death of us.
  - jaynetics 7y ago
    Well, you can go blind by overdosing it for a while ... Edit: but yes, this process will have to be simplified in every country if it turns out to be the primary recourse.
    - fhoe 7y ago
      > Well, you can go blind by overdosing it for a while ... A "while" here means months, or even years. In fact, many people with Lupus or RA take this for years.
  - the_watcher 7y ago
    It's at least (apparently) easy to produce and abundantly available in other countries. The medical system status quo is a challenge, but not having to stand up an entirely new production line is a big plus here.
  - ck2 7y ago
    Gatekeeping on antivirals is probably not a horrible idea. One terrible solution we have in the USA because we refuse to see healthcare as a right (omg we can't have everyone healthy or too healthy) is many states have practicing nurses as pseudo-doctors at some pharmacies (ie. CVS "Minute Clinic") where you give them $100 to be seen, and then they write a script. It's disgusting but it's a solution.
ck2 7y ago
That's hydroxychloroquine right? Same drug they use to treat lupus so it's well tested? edit: oh wait, maybe not https://www.ncbi.nlm.nih.gov/pubmed/32150618 https://www.ncbi.nlm.nih.gov/pubmed/32150618 Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro. If so, goodrx shows it's $20, hopefully it will spare some deaths. https://www.goodrx.com/hydroxychloroquine https://www.goodrx.com/hydroxychloroquine
- surewhynat 7y ago
  No, it is a relative to the drug. Although from what I understand is that they behave similarly. Someone posted a link to this useful video yesterday, https://www.youtube.com/watch?v=U7F1cnWup9M https://www.youtube.com/watch?v=U7F1cnWup9M edit: typo
- the_watcher 7y ago
  Chloroquine is a common anti-malarial and can be purchased OTC in much of Latin America.
theologic 7y ago
I am tremendously torn by this: a. We have multiple indications that this is an adjunct therapy that can help b. Humans are exceptionally easy to fool, and we know that placebos are incredibly effective because they trick our brain into creating chemicals. The placebo is so strong that we design double blind studies because we can't even trust the person giving the experiment. However, if it does help, it will be extremely encouraging. The critical thing is to get a double blind study with sufficient n to immediately make a choice. This is where having more resources do help because the safety of the drug, normally a massive bottleneck, is well understood.
- avip 7y ago
  You're missing the point that patients receiving this treatment are considered in a terminal condition and are likely on life-support (that is the only situation you could give an unapproved drug to a patient).
  - sgt101 7y ago
    Is it unapproved? I thought it was in widespread use as an anti-malarial (for 70 + years)?
    - 77pt77 7y ago
      It is widespread but this usage is off label.
  - DennisP 7y ago
    This is not an unapproved drug, just an off-label use. From wikipedia: > Chloroquine was discovered in 1934 by Hans Andersag.[3][4] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[5]
  - cm2187 7y ago
    Where did you see that this is for terminal conditions? Raoult suggested even patients with mild symptoms be treated with those molecules to reduce the contagion.
deleted 7y ago
[deleted]
oli5679 7y ago
Naive question, does this mean quinine may also help, and is there enough in tonic water to have any clinical effect?
- deleted 7y ago
  [deleted]
- jaynetics 7y ago
  1. Yes. 2. No, you'd have to drink like 30 liters a day.
- dheera 7y ago
  No. 1 liter of commercial tonic water has about 83 mg of quinine, and the typical dose for malaria treatment is 648 mg three times a day. You'd have to drink 23.4 liters of tonic water a day to get that amount of quinine, and you'd probably poison yourself from that amount of water and sugar.
  - nullc 7y ago
    These doses are quite high though because they are using them for treatment. Preventative doses of chloroquine for malaria are about 300mg per week. I'm not sure what preventative doses of quinine are typically, presumably much higher than chloroquine, but how much higher?
jeromebaek 7y ago
Explains why there's little outbreak in Africa.
- zaroth 7y ago
  Now that's an interesting theory...
- tim333 7y ago
  Probably not. It's available there but it's not like everyone is on the stuff.
- forkexec 7y ago
  No. Temperature has more to do with it, which has already been proven with the semi-log growth charts.
hprotagonist 7y ago
I have some meta-doubts about the linked presentation (https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...) 1. for starters, it's a random gdrive link not on medrxiv or biorxiv. why? 2. it's GPL3'd? Conventionally, we disseminate open access research as CC-BY 4. 3. the first author is who he says he is -- but he is a "managing partner" at blocktown capital not a practicing physician. [0] 4. The second author is a bioinformatics masters student who is also a lawyer and not obviously a practicing researcher. [1] 5. Figures 1 and 2 are presented without obvious attribution from https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69 https://virologyj.biomedcentral.com/articles/10.1186/1743-42..., which is not about SARS-CoV-2, but about the first SARS from 2002. This isn't my field, but i am a biomedical researcher and i'm very used to reading the medical literature, and this read deeply strangely in a lot of ways that are hard to quantify. The language isn't what I'd expect for a research paper, but it's kind of written like it wants to be one. I'm not super clear on what's going on. I have no reason to doubt the intentions of the authors, per se, but this work is super rough around the edges. It reads like a thrown-together collection of notes for a lab meeting, but not something I'd show off in public. [0]: https://twitter.com/JamesTodaroMD https://twitter.com/JamesTodaroMD [1]: https://www.riganollc.com/attorneys/gregory-j-rigano/ https://www.riganollc.com/attorneys/gregory-j-rigano/
- avip 7y ago
  I'm generally in agreement with you, but tangentially, Chloroquine was already tried in some countries (not in the controlled sense we expect in an actual clinical trial), and showed "promising results" https://sci-hub.si/https://www.sciencedirect.com/science/article/pii/S0166354220301145 https://sci-hub.si/https://www.sciencedirect.com/science/art...
  - hprotagonist 7y ago
    that is a much more comprehensibly written document. Nice find.
- capkutay 7y ago
ucha 7y ago
I listened to the linked video and read the article/papers. What I take from them is: - Chinese doctors initially tested chloroquine in-vitro on SARS-Cov-2 and it reduced the viral load significantly. Similar results were observed with other viruses including SARS-Cov. - They then tested it in-vivo (on patients) and it showed promising results - The speaker explains then that they had 3 cohorts of infected patients on which they tested daily for SARS-Cov-2. First cohort was the control (no treatment), second one received Plaquenil (hydroxychloroquine), third one received Plaquenil and azithromycin (an antibiotic). After 7 days 1st cohort had approximately 85% testing positive, 2nd 40%, 3rd 5%. One could be surprised by the use of an antibiotic but it apparently helps with fight opportunistic bacterial infection resulting from a viral pneumonia. He adds that for every recorded death, the patient tested positive for the virus before their death and concludes that if the double treatment of azythromicin + Plaquenil reduces the viral load, then it would improve patient prognosis. In conclusion, I think it's quite a big deal if it is confirmed that chloroquine can reduce contagiosity and improve outcomes. It's widely available, cheap and safe. Give it to everyone showing symptoms, individuals who were in contact with confirmed cases, medical professionals, and you'll surely reduce R0 significantly. video: https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_title https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_titl... pre-pub paper: https://www.sciencedirect.com/science/article/pii/S0924857920300820?via%3Dihub https://www.sciencedirect.com/science/article/pii/S092485792... ppt (last page is result of experiment mentioned above): https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20...
- aazaa 7y ago
  > last page is result of experiment mentioned above The last slide is a bibliography. The second to the last is a slide is in vitro results. There's not one shred of new clinical data in that presentation from what I can see. What's happened is that the OP has linked to an article making claims that are not supported from the slide deck or YouTube video.
  - ucha 7y ago
    You're mistaken. The last slide is, like I said, the result of the experiment, the second to last is the bibliography.
Gatsky 7y ago
The bottom line is there isn't any quality data. But there are a lot of clinical trials in patients going on, so there should be something more reliable in 4 weeks or so. The most relevant endpoint at this time is not viral clearance (which also has reliability issues), it is avoidance of severe disease requiring hospitalisation and respiratory support, in particular invasive ventilation. Also relevant is whether prophylactic treatment in people at high risk of infection, such as healthcare workers, is effective. The treatment courses are short, so the side effects of hydroxychloroquine are largely irrelevant under the circumstances.
netmonk 7y ago
Who cares ? Facts are Facts, penis is male, pussy is female...Some wont be happy with thoses facts too. But Reality is based on Facts.
nraynaud 7y ago
I saw a tweet by a MD recently saying that some preliminary explanation of the effect of the virus (something about heme) would also explain why chloroquine would work. There seem to be a web of low quality data going in a coherent direction.
ineedasername 7y ago
I wonder if quinine, a very similar drug, would have similar results. We already have industrial infrastructure in place to mass produce and disseminate quinine (tonic water) but would have to increase the amount in each bottle. Pure, unadulterated speculation though.
- ncmncm 7y ago
  Quinine has much worse side effects than chloroquine's. The amount of quinine in tonic water is very, very low, or it would not be allowed. Fun fact: the lifetime of chloroquine in the body is 1 to 2 months.
DoreenMichele 7y ago
I can readily believe this is helpful. It's related to quinine. I've used quinine for years to deal effectively with exposure to viral infections. I have a compromised immune system and get sick very easily. I do a lot of weird stuff. /Anecdata
tim333 7y ago
Good to see some progress. The more experimental research on this sort of stuff the better. It's still not clear if these sort of meds should be given early as soon as you get a temperature say, or wait till hospital, or how those options compare. I'm hoping there'll be some good result like giving it early means almost everyone recovers without hospital but then maybe that won't work. Test baby test! In fact this sort of stuff may be our biggest hope. Containment doesn't seem to be working, vaccines will likely take too long but treatments like say giving chloroquine on fever might reduce deaths from 1% to 0.1% or some such. But we won't know without experiment.
ncmncm 7y ago
I can't say whether the work reported is defensible, but I can say that (1) chloroquine is not available over the counter in the US as it is in many places, (2) it can be dangerous, even fatal if misused, and (3) it is available in the US in pet stores for treating aquariums. So, provided you only put it in the tank you swim in, you should be OK, but I don't know about the safety of chloroquine phosphate taken orally. Still, if you are on the down slide, it might be preferable to risk it, and also to have some on hand against such an event.
- Nettle2 7y ago
  Hydroxychloroquinine is the drug that my father received during World WarII to treat Malaria tropica. The high dose worked so well on him, that he never again had a malaria attack. But unfortunately he developed severe liver damage as a consequence of the high dose, from which he never completely recovered.
tim333 7y ago
Summary of the best bit: Viral load dropped to near zero in patients with azithromycin and hydroxychloroquine compared to not much change with the control group https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20... (graph at bottom)
Ace17 7y ago
No placebo for the control group? no double-blind? C'mon guys ... these kind of crisis are where strict scientific discipline is the most needed, because the risk of rushing to a false conclusion is higher. "but we don't have time, so we'll take whatever that seems to work" would be a valid argument if Chloroquine had zero negative side-effects. Which isn't the case.
CaveShadow 7y ago
New Paper just released by the same group: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial Gregory Rigano @RiganoESQ (posted to twitter 7am PDT 3/18/2020 Didier Raoult MD, PhD https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWS...
- Nettle2 7y ago
  Gregory Rigano ist a LAWYER who is trying to get a patent for Hydroxychloroquinine as Covid-19 treatment. This must be a complete fraud! Obviously someone with high fever during the infection will have his temperature lowered, since this is also the purpose of the drug during a malaria attack! Even if there is a real effect in vitro, if it doesn't work in vivo, it means nothing! The medical world is littered with unsuccessful in vivo attempts of in vitro successes!
sheighzam 7y ago
Studies show that hydroxychloroquinone- not chloroquine or chloroquine phosphate - is what's effective. It has less side effects if not used for a long period of time (>5 years, then serious liver and retinal damage can occur). Plaquenil, the brand, is 100% hydroxychloroquine (possibly hydroxychloroquinone sulfate, I'd have to check), which requires perfect dosing per patient, usually around 500mg/day for a typical adult. With the generic hydroxychloroquinone, there are fillers, so taking 600mg might be better off, but don't quote me. The problem is that hydroxyc. can have major interactions with antibiotics (which interests me, since Azithromycin is recommended in conjunction - perhaps its referring to Flouroquonines which are very dangerous to cartilage anyway by themselves (Levaquin,Cipro,etc.). Also, seizure meds psychiatric meds, acetaminophen, and blood pressure medicines can cause interactions. Hydroxychloroquinone can actually help with weight loss and lowering glucose levels. I think this sounds promising - not as a treatment per se, nor a vaccine, but a prophylactic at the first sign of symptoms. I suspect adding zinc might be helpful, but that's just my idea for clearing up infections sooner. I think the Azithromycin may be used to address any bacterial side effects to which the hydroxychloroquinone may leave the immune system more susceptible, such as eye problems and strep. Another reason I think early use of zinc may help. Anyway, this is interesting stuff. And it's so cheap - since it's already a generic, no "lawyer" can patent this to make money. I think they're just trying to find the treatment, and I'm grateful it's not big pharma!
sheighzam 7y ago
I wish I could find the study so take this with a grain of salt without my presenting that, but I'll do a search; it's also all in French. It was a double blind, peer reviewed, replicated study that suggested 400-500mg hydroxyquinone (NOT hydroxyquinone sulfate,nor chloroquine nor chloroquine phosphate) + azithromycin (Zithromax, Z-pack, etc.) + zinc was shown to be effective either once symptoms began to shorten the duration, or can be used as a prophylactic measure, preventing the disease altogether in medical personnel. Raoult was one of the scientists behind the study, which differed slightly from his other studies. There was has been a 100% success rate so far, and presently they are testing on a larger sample of those in the medical profession. I will try to find the link. Very interesting stuff on this page that I'll have to read through...
sheighzam 7y ago
I'm curious about the Tocilizumab/Actemra study, but it's extremely dangerous to the heart, so I'm interested in the dosages and time frame used Also curious about the Remdesivir studies...

219 points by jseliger 7y ago

RalfWausE 7y ago

This sounds really promising! I hope this report find its way to the officials...

raindeer3 7y ago
Form what I read the UK has already stopped all export of this drug.
- deleted 7y ago
  [deleted]
- jaynetics 7y ago
  Yes, alongside Aletra. Source: https://www.pharmaceutical-technology.com/comment/parallel-export-covid-19/ https://www.pharmaceutical-technology.com/comment/parallel-e...
- 77pt77 7y ago
  This is easy to synthesize and very cheap. It also has potentially irreversible side effects, namely retina damage.
  - stubish 7y ago
    Thankfully retina damage seems to only be from continual use. This is medication people have stayed on for decades. It seems pretty benign for just a few weeks, unlike many medications where the long term side effects can kick in after just months.

aazaa 7y ago

Call me skeptical. The details in this article are insufficient to draw many conclusions. There is no paper, although a YouTube video (in French) is linked. The article doesn't make it clear whether Raoult was being interviewed, or the information was taken from the video. The linked Google Doc (not regarding the study in question, despite another comment on this thread) summarizes results from other purported studies. Even then, this document itself appears to lack the usual signs of authenticity. Be careful about drawing conclusions because the details just aren't there. Details are everything in drug discovery. Edit: Then there's the vague language in the article. > “We were able to ascertain that patients who had not received Plaquenil (the drug containing hydroxychloroquine) were still contagious after six days, but of those that had received Plaquenil, after six days, only 25% were still contagious.” "Contagious" means nothing because AFAIK, there is no test for it. There is a PCR test being used around the world to detect the presence of viral RNA. So it's suspicious that an expert would be using the word "contagious," which implies the ability to transmit the virus under experimental conditions. And it gets worse. Have a look at the video linked in the article: https://www.mediterranee-infection.com/coronavirus-diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/ https://www.mediterranee-infection.com/coronavirus-diagnosti... First, it begins with a title that doesn't match the title of the speaker's slide deck. Second, judging from the slides the video appears to be about COVID-19 testing in general. There doesn't seem to be anything of substance about chloroquine anywhere. I don't speak French, so maybe there is something there. If so, the slide deck doesn't reflect it. And there's no way that a successful clinical trial of a COVID-19 drug would begin with basic introductory slides that everyone already knows. This just doesn't add up. I'm calling bullshit.

NotAnAccountNO 7y ago
This is the presentation Raoult gave yesterday, publication is coming next week. https://youtu.be/n4J8kydOvbc https://youtu.be/n4J8kydOvbc Link to the powerpoint. Please don't kill the IHU's servers though: it's all in french. https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20...
- 7y ago

mrob 7y ago

>Patients were given 600mcg per day for 10 days. Did they really mean micrograms or is this a mistranslation of milligrams? 600mcg is much lower than any dose I've heard of for other conditions.

ibejoeb 7y ago
I'm sure it's mg. There is a similar experiment from Melbourne that cites similar dosage. I'll try to find it. Also, it looks like there is a US clinical trial of chloriquine to start in May: https://clinicaltrials.gov/ct2/show/NCT04303507 https://clinicaltrials.gov/ct2/show/NCT04303507
ComputerGuru 7y ago
EDIT: this source [0] seems to confirm that it is indeed milligrams, but I don't understand how any of this jives with what I found earlier from the FDA on therapeutic index and overdosing. [0]: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj... See the original comment with my findings from the FDA below, however. --- I don't think it's a mistake. 600mg per day is 14x the recommended dosage for malarial suppression with cholorquine. Per the FDA, the dosage is 300mg of chloroquine per week for malarial suppression: > Adult Dose: 500 mg (=300 mg base) on exactly the same day of each week. For children: > The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight. Source: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/006002s043lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/00... Additionally, it seems that it is incredibly easy to fatally overdose on this: > Chloroquine is very rapidly and completely absorbed after ingestion. Toxic doses of chloroquine can be fatal. As little as 1 g may be fatal in children. Toxic symptoms can occur within minutes. These consist of headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, shock and convulsions followed by sudden and early respiratory and cardiac arrest. Hypokalemia has been observed with arrhythmias in cases of intoxication. The electrocardiogram may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, and progressive bradycardia leading to ventricular fibrillation and/or arrest. Cases of extrapyramidal disorders have also been reported in the context of chloroquine overdose (see WARNINGS and ADVERSE REACTIONS) See also this paper about known cases of overdose in kids: https://pediatrics.aappublications.org/content/27/1/95.long?sso=1&sso_redirect_count=1&nfstatus=401&nftoken=00000000-0000-0000-0000-000000000000&nfstatusdescription=ERROR%3a+No+local+token https://pediatrics.aappublications.org/content/27/1/95.long?... Note that is for all for cholorquine base, not chloroquine phosphate which is ~60% choloroquine.

shanxS 7y ago

From the article Paper: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj... Video(not in English): https://www.mediterranee-infection.com/coronavirus-diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/ https://www.mediterranee-infection.com/coronavirus-diagnosti...

bertil 7y ago
That researcher is likely, at best, controversial: - he starts by arguing against quarantine; his point is that it didn’t work for Cholera in 1832; - he dismisses two thirds of the efforts against HIV/AIDS: understanding transmission effort and promoting condoms, focusing on treatment lowering viral load; - he then moves on to framing response to the pandemic in a conspiracy-sounding “shift of power towards the Far East”; - he then says “most countries” have chosen to test extensively early — I don’t think that’s really true: South Korea, has but I don’t think many other did; - he’s surprisingly unmoved by mortality on the cruise boat ashore Japan; I know epidemiologists can seem comfortable with terrifying stats, but he’s more than that. He’s not terrible over all and fairly eloquent to make his case but I’d take his presentation with a grain of salt. Key points: - children don’t seem to be contagious (they are asymptomatic but vectors for the flu); - viral loads are more predictive than anything; - people appear contagious for 20 days; key point isn’t a fix duration but measuring viral load and isolating anyone with a high level; - the hospital has 143 samples, they are looking forward to comparing genes with symptoms. He’s happy that people are attacking him for advertising chloroquinine because the controversy drives traffic… Not sure most doctors would be confortable with that media strategy. He’s unhappy that television features people without qualification, though. He compares his findings with similar findings in China and Korea with slightly different treatment (600 mg vs 2x500 hydroxi-chloroquinine, which he claims to have been the first to propose for other infections). He uses patients from nearby town who didn’t receive the treatment in a quasi-experiment on the impact on viral-load duration. He’s also recommending a combination with an anti-biotic because complications are often microbial. His final point is to not recommend to go home but be tested and treated. I think that he’s onto something scientifically and he could be talking about it on TV but before that, he _needs_ to get some media training to focus on the positive.

fhoe 7y ago

The problem is patients only get this at the point that they require hospitalization. It should be as easy to get a short-term dose of this (unlikely to cause severe side effects) as it is to get a seasonal flu shot, and people should be advised to take it for two weeks (or whatever) at the onset of symptoms, or even as a prophylactic if they know they were exposed.

fhoe 7y ago
Instead of being able to order this from Amazon or Walmart online, you have to 1) go to a doctor, NP, or other medical practitioner with prescription power 2) convince them to write you the script (and pay them, directly or indirectly, for this service) 3) have it sent electronically (in NY) to the right pharmacy that can fill it 4) then go to the pharmacy and fill it The rent-seeking in our medical system will be the death of us.
- jaynetics 7y ago
  Well, you can go blind by overdosing it for a while ... Edit: but yes, this process will have to be simplified in every country if it turns out to be the primary recourse.
  - fhoe 7y ago
    > Well, you can go blind by overdosing it for a while ... A "while" here means months, or even years. In fact, many people with Lupus or RA take this for years.
- the_watcher 7y ago
  It's at least (apparently) easy to produce and abundantly available in other countries. The medical system status quo is a challenge, but not having to stand up an entirely new production line is a big plus here.
- ck2 7y ago
  Gatekeeping on antivirals is probably not a horrible idea. One terrible solution we have in the USA because we refuse to see healthcare as a right (omg we can't have everyone healthy or too healthy) is many states have practicing nurses as pseudo-doctors at some pharmacies (ie. CVS "Minute Clinic") where you give them $100 to be seen, and then they write a script. It's disgusting but it's a solution.

ck2 7y ago

That's hydroxychloroquine right? Same drug they use to treat lupus so it's well tested? edit: oh wait, maybe not https://www.ncbi.nlm.nih.gov/pubmed/32150618 https://www.ncbi.nlm.nih.gov/pubmed/32150618 Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro. If so, goodrx shows it's $20, hopefully it will spare some deaths. https://www.goodrx.com/hydroxychloroquine https://www.goodrx.com/hydroxychloroquine

surewhynat 7y ago
No, it is a relative to the drug. Although from what I understand is that they behave similarly. Someone posted a link to this useful video yesterday, https://www.youtube.com/watch?v=U7F1cnWup9M https://www.youtube.com/watch?v=U7F1cnWup9M edit: typo
the_watcher 7y ago
Chloroquine is a common anti-malarial and can be purchased OTC in much of Latin America.

theologic 7y ago

I am tremendously torn by this: a. We have multiple indications that this is an adjunct therapy that can help b. Humans are exceptionally easy to fool, and we know that placebos are incredibly effective because they trick our brain into creating chemicals. The placebo is so strong that we design double blind studies because we can't even trust the person giving the experiment. However, if it does help, it will be extremely encouraging. The critical thing is to get a double blind study with sufficient n to immediately make a choice. This is where having more resources do help because the safety of the drug, normally a massive bottleneck, is well understood.

avip 7y ago
You're missing the point that patients receiving this treatment are considered in a terminal condition and are likely on life-support (that is the only situation you could give an unapproved drug to a patient).
- sgt101 7y ago
  Is it unapproved? I thought it was in widespread use as an anti-malarial (for 70 + years)?
  - 77pt77 7y ago
    It is widespread but this usage is off label.
- DennisP 7y ago
  This is not an unapproved drug, just an off-label use. From wikipedia: > Chloroquine was discovered in 1934 by Hans Andersag.[3][4] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[5]
- cm2187 7y ago
  Where did you see that this is for terminal conditions? Raoult suggested even patients with mild symptoms be treated with those molecules to reduce the contagion.

deleted 7y ago

[deleted]

oli5679 7y ago

Naive question, does this mean quinine may also help, and is there enough in tonic water to have any clinical effect?

deleted 7y ago
[deleted]
jaynetics 7y ago
1. Yes. 2. No, you'd have to drink like 30 liters a day.
dheera 7y ago
No. 1 liter of commercial tonic water has about 83 mg of quinine, and the typical dose for malaria treatment is 648 mg three times a day. You'd have to drink 23.4 liters of tonic water a day to get that amount of quinine, and you'd probably poison yourself from that amount of water and sugar.
- nullc 7y ago
  These doses are quite high though because they are using them for treatment. Preventative doses of chloroquine for malaria are about 300mg per week. I'm not sure what preventative doses of quinine are typically, presumably much higher than chloroquine, but how much higher?

jeromebaek 7y ago

Explains why there's little outbreak in Africa.

zaroth 7y ago
Now that's an interesting theory...
tim333 7y ago
Probably not. It's available there but it's not like everyone is on the stuff.
forkexec 7y ago
No. Temperature has more to do with it, which has already been proven with the semi-log growth charts.

hprotagonist 7y ago

I have some meta-doubts about the linked presentation (https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...) 1. for starters, it's a random gdrive link not on medrxiv or biorxiv. why? 2. it's GPL3'd? Conventionally, we disseminate open access research as CC-BY 4. 3. the first author is who he says he is -- but he is a "managing partner" at blocktown capital not a practicing physician. [0] 4. The second author is a bioinformatics masters student who is also a lawyer and not obviously a practicing researcher. [1] 5. Figures 1 and 2 are presented without obvious attribution from https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69 https://virologyj.biomedcentral.com/articles/10.1186/1743-42..., which is not about SARS-CoV-2, but about the first SARS from 2002. This isn't my field, but i am a biomedical researcher and i'm very used to reading the medical literature, and this read deeply strangely in a lot of ways that are hard to quantify. The language isn't what I'd expect for a research paper, but it's kind of written like it wants to be one. I'm not super clear on what's going on. I have no reason to doubt the intentions of the authors, per se, but this work is super rough around the edges. It reads like a thrown-together collection of notes for a lab meeting, but not something I'd show off in public. [0]: https://twitter.com/JamesTodaroMD https://twitter.com/JamesTodaroMD [1]: https://www.riganollc.com/attorneys/gregory-j-rigano/ https://www.riganollc.com/attorneys/gregory-j-rigano/

avip 7y ago
I'm generally in agreement with you, but tangentially, Chloroquine was already tried in some countries (not in the controlled sense we expect in an actual clinical trial), and showed "promising results" https://sci-hub.si/https://www.sciencedirect.com/science/article/pii/S0166354220301145 https://sci-hub.si/https://www.sciencedirect.com/science/art...
- hprotagonist 7y ago
  that is a much more comprehensibly written document. Nice find.
capkutay 7y ago

ucha 7y ago

I listened to the linked video and read the article/papers. What I take from them is: - Chinese doctors initially tested chloroquine in-vitro on SARS-Cov-2 and it reduced the viral load significantly. Similar results were observed with other viruses including SARS-Cov. - They then tested it in-vivo (on patients) and it showed promising results - The speaker explains then that they had 3 cohorts of infected patients on which they tested daily for SARS-Cov-2. First cohort was the control (no treatment), second one received Plaquenil (hydroxychloroquine), third one received Plaquenil and azithromycin (an antibiotic). After 7 days 1st cohort had approximately 85% testing positive, 2nd 40%, 3rd 5%. One could be surprised by the use of an antibiotic but it apparently helps with fight opportunistic bacterial infection resulting from a viral pneumonia. He adds that for every recorded death, the patient tested positive for the virus before their death and concludes that if the double treatment of azythromicin + Plaquenil reduces the viral load, then it would improve patient prognosis. In conclusion, I think it's quite a big deal if it is confirmed that chloroquine can reduce contagiosity and improve outcomes. It's widely available, cheap and safe. Give it to everyone showing symptoms, individuals who were in contact with confirmed cases, medical professionals, and you'll surely reduce R0 significantly. video: https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_title https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_titl... pre-pub paper: https://www.sciencedirect.com/science/article/pii/S0924857920300820?via%3Dihub https://www.sciencedirect.com/science/article/pii/S092485792... ppt (last page is result of experiment mentioned above): https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20...

aazaa 7y ago
> last page is result of experiment mentioned above The last slide is a bibliography. The second to the last is a slide is in vitro results. There's not one shred of new clinical data in that presentation from what I can see. What's happened is that the OP has linked to an article making claims that are not supported from the slide deck or YouTube video.
- ucha 7y ago
  You're mistaken. The last slide is, like I said, the result of the experiment, the second to last is the bibliography.

Gatsky 7y ago

The bottom line is there isn't any quality data. But there are a lot of clinical trials in patients going on, so there should be something more reliable in 4 weeks or so. The most relevant endpoint at this time is not viral clearance (which also has reliability issues), it is avoidance of severe disease requiring hospitalisation and respiratory support, in particular invasive ventilation. Also relevant is whether prophylactic treatment in people at high risk of infection, such as healthcare workers, is effective. The treatment courses are short, so the side effects of hydroxychloroquine are largely irrelevant under the circumstances.

netmonk 7y ago

Who cares ? Facts are Facts, penis is male, pussy is female...Some wont be happy with thoses facts too. But Reality is based on Facts.

nraynaud 7y ago

I saw a tweet by a MD recently saying that some preliminary explanation of the effect of the virus (something about heme) would also explain why chloroquine would work. There seem to be a web of low quality data going in a coherent direction.

ineedasername 7y ago

I wonder if quinine, a very similar drug, would have similar results. We already have industrial infrastructure in place to mass produce and disseminate quinine (tonic water) but would have to increase the amount in each bottle. Pure, unadulterated speculation though.

ncmncm 7y ago
Quinine has much worse side effects than chloroquine's. The amount of quinine in tonic water is very, very low, or it would not be allowed. Fun fact: the lifetime of chloroquine in the body is 1 to 2 months.

DoreenMichele 7y ago

I can readily believe this is helpful. It's related to quinine. I've used quinine for years to deal effectively with exposure to viral infections. I have a compromised immune system and get sick very easily. I do a lot of weird stuff. /Anecdata

tim333 7y ago

Good to see some progress. The more experimental research on this sort of stuff the better. It's still not clear if these sort of meds should be given early as soon as you get a temperature say, or wait till hospital, or how those options compare. I'm hoping there'll be some good result like giving it early means almost everyone recovers without hospital but then maybe that won't work. Test baby test! In fact this sort of stuff may be our biggest hope. Containment doesn't seem to be working, vaccines will likely take too long but treatments like say giving chloroquine on fever might reduce deaths from 1% to 0.1% or some such. But we won't know without experiment.

ncmncm 7y ago

I can't say whether the work reported is defensible, but I can say that (1) chloroquine is not available over the counter in the US as it is in many places, (2) it can be dangerous, even fatal if misused, and (3) it is available in the US in pet stores for treating aquariums. So, provided you only put it in the tank you swim in, you should be OK, but I don't know about the safety of chloroquine phosphate taken orally. Still, if you are on the down slide, it might be preferable to risk it, and also to have some on hand against such an event.

Nettle2 7y ago
Hydroxychloroquinine is the drug that my father received during World WarII to treat Malaria tropica. The high dose worked so well on him, that he never again had a malaria attack. But unfortunately he developed severe liver damage as a consequence of the high dose, from which he never completely recovered.

tim333 7y ago

Summary of the best bit: Viral load dropped to near zero in patients with azithromycin and hydroxychloroquine compared to not much change with the control group https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf https://www.mediterranee-infection.com/wp-content/uploads/20... (graph at bottom)

Ace17 7y ago

No placebo for the control group? no double-blind? C'mon guys ... these kind of crisis are where strict scientific discipline is the most needed, because the risk of rushing to a false conclusion is higher. "but we don't have time, so we'll take whatever that seems to work" would be a valid argument if Chloroquine had zero negative side-effects. Which isn't the case.

CaveShadow 7y ago

New Paper just released by the same group: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial Gregory Rigano @RiganoESQ (posted to twitter 7am PDT 3/18/2020 Didier Raoult MD, PhD https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWS...

Nettle2 7y ago
Gregory Rigano ist a LAWYER who is trying to get a patent for Hydroxychloroquinine as Covid-19 treatment. This must be a complete fraud! Obviously someone with high fever during the infection will have his temperature lowered, since this is also the purpose of the drug during a malaria attack! Even if there is a real effect in vitro, if it doesn't work in vivo, it means nothing! The medical world is littered with unsuccessful in vivo attempts of in vitro successes!

sheighzam 7y ago

Studies show that hydroxychloroquinone- not chloroquine or chloroquine phosphate - is what's effective. It has less side effects if not used for a long period of time (>5 years, then serious liver and retinal damage can occur). Plaquenil, the brand, is 100% hydroxychloroquine (possibly hydroxychloroquinone sulfate, I'd have to check), which requires perfect dosing per patient, usually around 500mg/day for a typical adult. With the generic hydroxychloroquinone, there are fillers, so taking 600mg might be better off, but don't quote me. The problem is that hydroxyc. can have major interactions with antibiotics (which interests me, since Azithromycin is recommended in conjunction - perhaps its referring to Flouroquonines which are very dangerous to cartilage anyway by themselves (Levaquin,Cipro,etc.). Also, seizure meds psychiatric meds, acetaminophen, and blood pressure medicines can cause interactions. Hydroxychloroquinone can actually help with weight loss and lowering glucose levels. I think this sounds promising - not as a treatment per se, nor a vaccine, but a prophylactic at the first sign of symptoms. I suspect adding zinc might be helpful, but that's just my idea for clearing up infections sooner. I think the Azithromycin may be used to address any bacterial side effects to which the hydroxychloroquinone may leave the immune system more susceptible, such as eye problems and strep. Another reason I think early use of zinc may help. Anyway, this is interesting stuff. And it's so cheap - since it's already a generic, no "lawyer" can patent this to make money. I think they're just trying to find the treatment, and I'm grateful it's not big pharma!

sheighzam 7y ago

I wish I could find the study so take this with a grain of salt without my presenting that, but I'll do a search; it's also all in French. It was a double blind, peer reviewed, replicated study that suggested 400-500mg hydroxyquinone (NOT hydroxyquinone sulfate,nor chloroquine nor chloroquine phosphate) + azithromycin (Zithromax, Z-pack, etc.) + zinc was shown to be effective either once symptoms began to shorten the duration, or can be used as a prophylactic measure, preventing the disease altogether in medical personnel. Raoult was one of the scientists behind the study, which differed slightly from his other studies. There was has been a 100% success rate so far, and presently they are testing on a larger sample of those in the medical profession. I will try to find the link. Very interesting stuff on this page that I'll have to read through...

sheighzam 7y ago

I'm curious about the Tocilizumab/Actemra study, but it's extremely dangerous to the heart, so I'm interested in the dosages and time frame used Also curious about the Remdesivir studies...