12 ms·

Personally I'm witholding judgment until the results of the PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT

Personally I'm witholding judgment until the results of the PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923) arrive, as it'll finally give us some decent statistical power, and be a full, double-blind RCT. It also has multiple study arms (health-care worker prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late, as some are now suggesting, we should finally know with some degree of certainty.

koheripbal 6y ago
Yeah, the devil is really in the details about exactly when and how you administer it. Doctors are already saying that it's definitely no magic bullet, but they debate whether it is effective at a certain stage of illness. What I don't understand is why we're focusing so much on this specific drug when there are some great antivirals out thee that have a more effective theoretical mechanism of action. (eg Remdesivir)
- simcop2387 6y ago
  It's being focused on in the news, but the others are also being tested. The big problem is like the GP raised, we need proper testing to really be able to say much about the ability of any of these drugs to help. [1] https://www.fiercebiotech.com/biotech/gilead-clinical-data-hint-at-efficacy-remdesivir-covid-19 https://www.fiercebiotech.com/biotech/gilead-clinical-data-h...
- frgtpsswrdlame 6y ago
  Because this drug can be cheaply manufactured out of patent. Let's say Remdesivir is the only drug that works, it's basically an admission that Gilead is going to have us over a barrel.
  - munk-a 6y ago
    Only if we chose to let them bend us over said barrel? The US government could simply seize the patent if Gilead acted in a manner against the public good.
    - lonelappde 6y ago
      The US government is not "we", even if we are in the US.
    - tomohawk 6y ago
      And then what happens next time? Why spend all the time and effort, only to have what you did nationalized? Incentivizing people to not do productive things like develop drugs seems like a really bad idea.
      - sadfklsjlkjwt 6y ago
        I used to agree with you. Then I realized that drug companies spend more on lawyers than scientists.
        _n_b_ 6y ago
        This isn’t even remotely close to true. 0.67% on legal[1] versus 17% on R&D[2]. [1] https://ccbjournal.com/articles/benchmark-metrics-pharma-companies-indexing-allows-cross-industry-law-department-comp https://ccbjournal.com/articles/benchmark-metrics-pharma-com... [2] https://www.investopedia.com/ask/answers/060115/how-much-drug-companys-spending-allocated-research-and-development-average.asp https://www.investopedia.com/ask/answers/060115/how-much-dru...
        FireBeyond 6y ago
        And how much on marketing?
        sadfklsjlkjwt 6y ago
        You are right of course. My mistake. Marketing is where they spend their money!
  - subsubzero 6y ago
    > it's basically an admission that Gilead is going to have us over a barrel That's absolutely not what would happen. I was chatting with a family member who used to work in biotech/pharma and posed the question what would happen if Remdesivir is found to have efficacy against covid-19. What they said is basically there would be licensing done immediately to other pharma companies which would run manufacturing in parallel with what Gilead is doing. Gilead will be getting profits from each pharma company that gets a license. I am unsure why the lead time is so long, however it may be that the company does not want to create a huge supply of a drug that may not be effective. But this is very interesting, the pentagon is getting lots of remdesivir for troops so there must be some info that leadership has about its success rate: https://qz.com/1834939/how-the-military-secured-experimental-covid-19-drug-remdesivir/ https://qz.com/1834939/how-the-military-secured-experimental...
- hjnilsson 6y ago
  Remdesivir (and other antivirals / T-inhibitors on trial) are all extremely difficult to manufacture (and expensive) compared to hydroxychloroquine. Most hospitals and countries will be unable to acquire the amounts required for even small trials. It will be many months before we can begin to see results for these drugs.
- johntb86 6y ago
  Remdesivir could be great, and there are a lot of studies ongoing about it. However, it has a long production time - Gilead says 6 to 8 months: see https://www.gilead.com/purpose/advancing-global-health/covid-19/working-to-supply-remdesivir-for-covid-19 https://www.gilead.com/purpose/advancing-global-health/covid.... They're only projecting to have 500,000 treatment courses by October, so it could only help a relatively small fraction of the people that will have coronavirus.
  - smacktoward 6y ago
    Even a small volume of an effective treatment could still be helpful. Usage could be restricted just to patients with cases serious enough to otherwise require ventilators, for instance, which would both ease the strain on limited ICU resources and save lots of people who would otherwise die (since only around 10-30% of ventilated patients survive even with that treatment).
    - gvjddbnvdrbv 6y ago
      But antivirals tend to need to be given early to have a good effect. How will be know who is going to be severe?
      - roywiggins 6y ago
        By the time we have lots of it, we will have good statistics on demographics of people most likely to need it, so you could make educated guesses and still see a benefit.
        randcraw 6y ago
        To offer some perspective, in Montgomery County, just north of Philly (a suburban metro county harder hit than most), 10% of positive tests have been admitted to hospital, and 2.6% of positive tests have gone on ventilators. So the subpopulation needing remdesivir is probably less than 5% of the positive cases (or 1250 of the 25,000 who tested positive here). BTW, the county population is 900,000.
- lonelappde 6y ago
  Because it's become an arbitrary political football to separate "left" vs "right"
  - SlowRobotAhead 6y ago
    As insane as that is. And how funny is it (at least to me) that this is only because Trump came down on one side initially. If he had come out saying exactly the opposite, that HCQ was bad and we should be skeptical, everyone hoping it doesn’t work now would be looking for the 10 person studies saying it totally works and defending its use. It’s almost beyond reason how hyper partisan this specific issue is.
    - lalaland1125 6y ago
      The fundamental difference is that one side is backed by neutral experts such as Anthony Fauci and the other side has shown nothing but disdain for science in countless issues (global warming, evolution, election fraud, etc).
      - Bendingo 6y ago
        > neutral experts such as Anthony Fauci Fauci isn't close to being a neutral expert.
      - SlowRobotAhead 6y ago
        Sorry, I don’t buy into pole riding / hero worship, nor do I believe that theoretical-you on the theoretical-“other side” wouldn’t have an equal but opposing argument. It’s all game, do you really not see that? ... If you’ve been following this topic, shouldn’t you be able to make the steelman argument for it?
    - rsynnott 6y ago
      This isn't left vs right; it's an unqualified politician vs pretty much all of the scientific community.
      - 6y ago
- dTal 6y ago
  Because it's easy to make, there's tons of it lying around already, and it doesn't need human safety trials (we already know safe dosages). If it works, it'll be a near-miracle.
  - SiempreViernes 6y ago
    No, that explains the initial attention, not the sustained attention in the face of clear and severe problems it is now getting.
- ldng 6y ago
  They always were saying it wasn't magic bullet, but some people did not keep the context and started to spread only part of the story.
dessant 6y ago
> Estimated Primary Completion Date: April 1, 2021 Can we expect preliminary data from this trial before the primary completion date?
- apendleton 6y ago
  Yes, different arms will have data available at different times. The prophylaxis one might take longer than the others, but for the ones involving sick people, once they hit their target enrollment (which probably won't take long at all), those people will either get better or they won't.
  - Reelin 6y ago
    I wouldn't expect a given prophylaxis case to take more than ~2 weeks to assess (the recommended quarantine time), and I would expect there to be significantly more eligible participants for that arm than the others. Am I missing something?
    - apendleton 6y ago
      Prophylaxis is for people who are currently negative (it's pre-exposure, not post). You need to give them the medication (or a placebo) and then wait long enough for a significant fraction of each group to have had an opportunity to become infected, so you can meaningfully compare the trial group with the control group. They're all wearing PPE and such anyway (both groups), so not that many are going to seroconvert even in the control group in just a couple of weeks.
      - Reelin 6y ago
        I don't see how any of this would increase the time to evaluate a given study participant beyond ~2 weeks? Regarding what you said about prophylaxis, the study page specifies that participants will either: * Have had close contact with a known positive individual within the past 4 days (but not have any symptoms themselves yet). * Have developed symptoms (and tested positive) within the past 4 days. Technically that's not really a prophylaxis, but it's early enough that it's practically the same thing. It's also more representative of how we would be likely to employ the medication in the real world. (Also I don't see how it would be ethical to intentionally expose people, and waiting for people to be inadvertently exposed seems impractical for a number of reasons). Edit: Whoops. I had slightly confused the smaller PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923) and the larger University of Minnesota one (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668). It looks like the PATCH trial is indeed only testing actual prophylaxis in healthcare workers, and specifies a two month period for each participant in the trial.
programmarchy 6y ago
That link says the primary completion date won't be until April 1, 2021, a year from now. Seems like we should be able to collect valuable information much sooner than that because of the volume of patients, right?
majormajor 6y ago
> so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late What's the mechanism supposed to be here? If it suppresses replication of the virus, shouldn't that be effective up to close to the point of death - once replication is slowed enough, viral load should fall off, and recovery should happen?
- anoncareer0212 6y ago
  Hydroxycholorquine is an immunosuppresant not an anti-viral, so the theory here is the problem isn't the virus, but reacting to it. It's not quite as silly as it sounds - this does, rarely, work, specifically with malaria. But, it is pretty silly when you contrast the likelihood of it being a meaningful thereapeutic versus the significance it's taken on
  - edoo 6y ago
    From my understanding it does something to the virus membrane which then allows a high dose of zinc to actually disrupt the virus. I think the antibiotic component is to suppress risk of a secondary infection due to the suppressant effect.
    - dTal 6y ago
      I have heard (provenance rating: "rumour") that it's only effective when taken in conjunction with zinc supplementation.
  - jdkee 6y ago
    This is the popular origin of the hydroxycloroquine and zinc thesis. https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDInv_zLVFTgXA8tW0Mf1iiuuM_&index=36&t=0s https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDIn...
    - Gibbon1 6y ago
      Part of the reason I'm suspicious of hydroxycloroquine and zinc is because for decades zinc and cloroquine have been fringe quack medicine staples for treating/preventing colds and flu.
edoo 6y ago
They should have data already on this. Basically, is the current rather large population of people already taking HQC under representing in the Covid-19 patient data.
atourgates 6y ago
Are any large(r) scale trials incorporating Azithromycin as well? The "most promising" study I saw early on was this one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/ - which seemed to suggest that the combo eliminated the viral load in 3-5 days. The only followup study I've found was this one: https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1 https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v... - that urged caution with the combo because of a possibility of increased heart failure. Obviously, that's a very small study with
- giardini 6y ago
  Other antibiotics than azithromycin have been used, e.g., doxycycline. The antibiotic's purpose is to halt opportunistic bacterial infection; many antibiotics are available to do that.
  - robbiep 6y ago
    But azithromycin has an ACE2 inhibitory effect and its use in disease modulation is postulated to decrease viral entry to the cell in a similar mechanism to HCQ, hence the discussion of dual therapy there. The opportunistic bacterial infection is separate (although you’re correct that it has a role here)
- Reelin 6y ago
  The preprint you linked (https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1 https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v...) is a huge analysis based on historical health records (> 300k per condition). > Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment. Based on that, azithromycin would appear to be a decidedly bad choice of antibiotic to use in conjunction with HCQ. Luckily there are many others available. Derek Lowe has a recent and much more detailed analysis of all of this. (https://blogs.sciencemag.org/pipeline/archives/2020/04/11/the-latest-hydroxychloroquine-data-as-of-april-11 https://blogs.sciencemag.org/pipeline/archives/2020/04/11/th...)
3fe9a03ccd14ca5 6y ago
Completion date: April 1st 2021. Too little too late for much of the country.
deleted 6y ago
[deleted]

koheripbal 6y ago

Yeah, the devil is really in the details about exactly when and how you administer it. Doctors are already saying that it's definitely no magic bullet, but they debate whether it is effective at a certain stage of illness. What I don't understand is why we're focusing so much on this specific drug when there are some great antivirals out thee that have a more effective theoretical mechanism of action. (eg Remdesivir)

simcop2387 6y ago
It's being focused on in the news, but the others are also being tested. The big problem is like the GP raised, we need proper testing to really be able to say much about the ability of any of these drugs to help. [1] https://www.fiercebiotech.com/biotech/gilead-clinical-data-hint-at-efficacy-remdesivir-covid-19 https://www.fiercebiotech.com/biotech/gilead-clinical-data-h...
frgtpsswrdlame 6y ago
Because this drug can be cheaply manufactured out of patent. Let's say Remdesivir is the only drug that works, it's basically an admission that Gilead is going to have us over a barrel.
- munk-a 6y ago
  Only if we chose to let them bend us over said barrel? The US government could simply seize the patent if Gilead acted in a manner against the public good.
  - lonelappde 6y ago
    The US government is not "we", even if we are in the US.
  - tomohawk 6y ago
    And then what happens next time? Why spend all the time and effort, only to have what you did nationalized? Incentivizing people to not do productive things like develop drugs seems like a really bad idea.
    - sadfklsjlkjwt 6y ago
      I used to agree with you. Then I realized that drug companies spend more on lawyers than scientists.
      - _n_b_ 6y ago
        This isn’t even remotely close to true. 0.67% on legal[1] versus 17% on R&D[2]. [1] https://ccbjournal.com/articles/benchmark-metrics-pharma-companies-indexing-allows-cross-industry-law-department-comp https://ccbjournal.com/articles/benchmark-metrics-pharma-com... [2] https://www.investopedia.com/ask/answers/060115/how-much-drug-companys-spending-allocated-research-and-development-average.asp https://www.investopedia.com/ask/answers/060115/how-much-dru...
        FireBeyond 6y ago
        And how much on marketing?
        sadfklsjlkjwt 6y ago
        You are right of course. My mistake. Marketing is where they spend their money!
- subsubzero 6y ago
  > it's basically an admission that Gilead is going to have us over a barrel That's absolutely not what would happen. I was chatting with a family member who used to work in biotech/pharma and posed the question what would happen if Remdesivir is found to have efficacy against covid-19. What they said is basically there would be licensing done immediately to other pharma companies which would run manufacturing in parallel with what Gilead is doing. Gilead will be getting profits from each pharma company that gets a license. I am unsure why the lead time is so long, however it may be that the company does not want to create a huge supply of a drug that may not be effective. But this is very interesting, the pentagon is getting lots of remdesivir for troops so there must be some info that leadership has about its success rate: https://qz.com/1834939/how-the-military-secured-experimental-covid-19-drug-remdesivir/ https://qz.com/1834939/how-the-military-secured-experimental...
hjnilsson 6y ago
Remdesivir (and other antivirals / T-inhibitors on trial) are all extremely difficult to manufacture (and expensive) compared to hydroxychloroquine. Most hospitals and countries will be unable to acquire the amounts required for even small trials. It will be many months before we can begin to see results for these drugs.
johntb86 6y ago
Remdesivir could be great, and there are a lot of studies ongoing about it. However, it has a long production time - Gilead says 6 to 8 months: see https://www.gilead.com/purpose/advancing-global-health/covid-19/working-to-supply-remdesivir-for-covid-19 https://www.gilead.com/purpose/advancing-global-health/covid.... They're only projecting to have 500,000 treatment courses by October, so it could only help a relatively small fraction of the people that will have coronavirus.
- smacktoward 6y ago
  Even a small volume of an effective treatment could still be helpful. Usage could be restricted just to patients with cases serious enough to otherwise require ventilators, for instance, which would both ease the strain on limited ICU resources and save lots of people who would otherwise die (since only around 10-30% of ventilated patients survive even with that treatment).
  - gvjddbnvdrbv 6y ago
    But antivirals tend to need to be given early to have a good effect. How will be know who is going to be severe?
    - roywiggins 6y ago
      By the time we have lots of it, we will have good statistics on demographics of people most likely to need it, so you could make educated guesses and still see a benefit.
      - randcraw 6y ago
        To offer some perspective, in Montgomery County, just north of Philly (a suburban metro county harder hit than most), 10% of positive tests have been admitted to hospital, and 2.6% of positive tests have gone on ventilators. So the subpopulation needing remdesivir is probably less than 5% of the positive cases (or 1250 of the 25,000 who tested positive here). BTW, the county population is 900,000.
lonelappde 6y ago
Because it's become an arbitrary political football to separate "left" vs "right"
- SlowRobotAhead 6y ago
  As insane as that is. And how funny is it (at least to me) that this is only because Trump came down on one side initially. If he had come out saying exactly the opposite, that HCQ was bad and we should be skeptical, everyone hoping it doesn’t work now would be looking for the 10 person studies saying it totally works and defending its use. It’s almost beyond reason how hyper partisan this specific issue is.
  - lalaland1125 6y ago
    The fundamental difference is that one side is backed by neutral experts such as Anthony Fauci and the other side has shown nothing but disdain for science in countless issues (global warming, evolution, election fraud, etc).
    - Bendingo 6y ago
      > neutral experts such as Anthony Fauci Fauci isn't close to being a neutral expert.
    - SlowRobotAhead 6y ago
      Sorry, I don’t buy into pole riding / hero worship, nor do I believe that theoretical-you on the theoretical-“other side” wouldn’t have an equal but opposing argument. It’s all game, do you really not see that? ... If you’ve been following this topic, shouldn’t you be able to make the steelman argument for it?
  - rsynnott 6y ago
    This isn't left vs right; it's an unqualified politician vs pretty much all of the scientific community.
    - 6y ago
dTal 6y ago
Because it's easy to make, there's tons of it lying around already, and it doesn't need human safety trials (we already know safe dosages). If it works, it'll be a near-miracle.
- SiempreViernes 6y ago
  No, that explains the initial attention, not the sustained attention in the face of clear and severe problems it is now getting.
ldng 6y ago
They always were saying it wasn't magic bullet, but some people did not keep the context and started to spread only part of the story.

dessant 6y ago

> Estimated Primary Completion Date: April 1, 2021 Can we expect preliminary data from this trial before the primary completion date?

apendleton 6y ago
Yes, different arms will have data available at different times. The prophylaxis one might take longer than the others, but for the ones involving sick people, once they hit their target enrollment (which probably won't take long at all), those people will either get better or they won't.
- Reelin 6y ago
  I wouldn't expect a given prophylaxis case to take more than ~2 weeks to assess (the recommended quarantine time), and I would expect there to be significantly more eligible participants for that arm than the others. Am I missing something?
  - apendleton 6y ago
    Prophylaxis is for people who are currently negative (it's pre-exposure, not post). You need to give them the medication (or a placebo) and then wait long enough for a significant fraction of each group to have had an opportunity to become infected, so you can meaningfully compare the trial group with the control group. They're all wearing PPE and such anyway (both groups), so not that many are going to seroconvert even in the control group in just a couple of weeks.
    - Reelin 6y ago
      I don't see how any of this would increase the time to evaluate a given study participant beyond ~2 weeks? Regarding what you said about prophylaxis, the study page specifies that participants will either: * Have had close contact with a known positive individual within the past 4 days (but not have any symptoms themselves yet). * Have developed symptoms (and tested positive) within the past 4 days. Technically that's not really a prophylaxis, but it's early enough that it's practically the same thing. It's also more representative of how we would be likely to employ the medication in the real world. (Also I don't see how it would be ethical to intentionally expose people, and waiting for people to be inadvertently exposed seems impractical for a number of reasons). Edit: Whoops. I had slightly confused the smaller PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923) and the larger University of Minnesota one (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668). It looks like the PATCH trial is indeed only testing actual prophylaxis in healthcare workers, and specifies a two month period for each participant in the trial.

programmarchy 6y ago

That link says the primary completion date won't be until April 1, 2021, a year from now. Seems like we should be able to collect valuable information much sooner than that because of the volume of patients, right?

majormajor 6y ago

> so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late What's the mechanism supposed to be here? If it suppresses replication of the virus, shouldn't that be effective up to close to the point of death - once replication is slowed enough, viral load should fall off, and recovery should happen?

anoncareer0212 6y ago
Hydroxycholorquine is an immunosuppresant not an anti-viral, so the theory here is the problem isn't the virus, but reacting to it. It's not quite as silly as it sounds - this does, rarely, work, specifically with malaria. But, it is pretty silly when you contrast the likelihood of it being a meaningful thereapeutic versus the significance it's taken on
- edoo 6y ago
  From my understanding it does something to the virus membrane which then allows a high dose of zinc to actually disrupt the virus. I think the antibiotic component is to suppress risk of a secondary infection due to the suppressant effect.
  - dTal 6y ago
    I have heard (provenance rating: "rumour") that it's only effective when taken in conjunction with zinc supplementation.
- jdkee 6y ago
  This is the popular origin of the hydroxycloroquine and zinc thesis. https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDInv_zLVFTgXA8tW0Mf1iiuuM_&index=36&t=0s https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDIn...
  - Gibbon1 6y ago
    Part of the reason I'm suspicious of hydroxycloroquine and zinc is because for decades zinc and cloroquine have been fringe quack medicine staples for treating/preventing colds and flu.

edoo 6y ago

They should have data already on this. Basically, is the current rather large population of people already taking HQC under representing in the Covid-19 patient data.

atourgates 6y ago

Are any large(r) scale trials incorporating Azithromycin as well? The "most promising" study I saw early on was this one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/ - which seemed to suggest that the combo eliminated the viral load in 3-5 days. The only followup study I've found was this one: https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1 https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v... - that urged caution with the combo because of a possibility of increased heart failure. Obviously, that's a very small study with

giardini 6y ago
Other antibiotics than azithromycin have been used, e.g., doxycycline. The antibiotic's purpose is to halt opportunistic bacterial infection; many antibiotics are available to do that.
- robbiep 6y ago
  But azithromycin has an ACE2 inhibitory effect and its use in disease modulation is postulated to decrease viral entry to the cell in a similar mechanism to HCQ, hence the discussion of dual therapy there. The opportunistic bacterial infection is separate (although you’re correct that it has a role here)
Reelin 6y ago
The preprint you linked (https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1 https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v...) is a huge analysis based on historical health records (> 300k per condition). > Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment. Based on that, azithromycin would appear to be a decidedly bad choice of antibiotic to use in conjunction with HCQ. Luckily there are many others available. Derek Lowe has a recent and much more detailed analysis of all of this. (https://blogs.sciencemag.org/pipeline/archives/2020/04/11/the-latest-hydroxychloroquine-data-as-of-april-11 https://blogs.sciencemag.org/pipeline/archives/2020/04/11/th...)

3fe9a03ccd14ca5 6y ago

Completion date: April 1st 2021. Too little too late for much of the country.

deleted 6y ago

[deleted]