New study on Hydroxychloroquine with Azithromycin, failure

[blueash]

There have been many threads pushing hydroxychloroquine with and without azithromycin. This combination has been touted by many here and by some elsewhere as having been proven. I have participated in the TOTV threads cautioning that the data are not clear and more studies are being done.

One is now ready for publication (https://pdf.sciencedirectassets.com/272288/AIP/1-s2.0-S0399077X20300858/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjECkaCXVzLWVhc3QtMSJHMEUCIQDR DvWeUwiwp%2F6SpknE6xlD5iSILxS%2BfsYVa08Ty4xwOwIgCB NaYgYB8i2L80b%2BdcAtn8fRIa6GKmxtMADcDL7wJ8sqtAMIMh ACGgwwNTkwMDM1NDY4NjUiDEya8bjpVeLE1F9nQiqRA9muxOqg Gz%2BDnVG9JxdCgzPvmgmlFBd6YjrIZwxleD%2BVD89JIfiyrT rP7X5e2h%2Fk0MJ62QmqCDxuy89y1woqnNCgD5CboQ3VIsOboS DsX8Aag3JHRLnevfz6hrJR1ouTDUjckhzs1Zp48KZa7ejkU9BT jrmvyIWCdTfzz%2BUWb2vlhBtPZ6WJfJOiPyXcH3hUV0WHpaQm 0T9NNyZFVcG6%2BhpzDbwOIF7HOSTPAeit%2BEs40bRMEalSBI ReUphDdecviHWnMDVF1VNlLzqKwaPMJusWbDEMUWmxJ%2BZyKR B5J7yzGScIHXxQExVcmuRDglvcBH%2Bl5ZosGIEB8PjhlX5Xk5 ZoKpk5wiihlxfAgZzgzwyidhrejin6U8zJJAZuJh5RBnd2xf4% 2BU5hf0pAgxL75cKVzmNxVLCS9d7B1wrOZl6FuFnIjTam%2Far KRcnkQpeclw1UOZpJU7lbsNU2gFpUsmyrphbXNpqGnunMJxjnF JDWUtOClztW%2BnzV22IY4jH2njnEJf%2BoCDFTuSFJmr9oh5T CGMI%2BJk%2FQFOusBYgv3SI6TCw2d%2Bbl9Fz0YrmdRMWY%2F tY5OZlFpDSxkaKyRlWzowe%2B0ZOCMB6Gu1XMVAfVXdHDok9D3 A4auOR7%2BsXbXZWFWbpp51qq0ANAfcPfzORgul5EXMU85G0C% 2FEJvQ%2FYHcJcnYcvELAaulZ41y1b%2FSEOQFm1frjgw3W%2B %2BFLU0ucPTdAD1bKZhy%2BVSEpAO%2B247l9s64fvQSAlt%2B TWJyRxgXBTaKN9Izm%2FnOUFUTw2XO9IgPRUjApKF4lKY88mkC EvpQt1rp0qBdUSwbSHqdmKWdwOYuzUK6pAfajq9xF%2FjnprsX ChCDh%2BypUA%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200401T174718Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYVYI6JHKZ%2F20200401%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=9d5a465dd29bfe1db438bec72a086ae6e01957fc 3d590f854eba587b3a863cba&hash=63ce08950c07b11e582d87977671fea1f9a0162273453 05f1708877d0e5a0d8b&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd08 6a07176afe7c76c2c61&pii=S0399077X20300858&tid=spdf-9c42051d-9caf-4f64-82f0-29e8efd2be81&sid=d29e890e8cf6224ff108c23972ccda67b0e4gxrqa&type=client). Like the one that started it all, this is from France. It looked at 11 patients in Paris to attempt to replicate the earlier study where it was claimed that 6 of 6 patients given the combination had no virus detected after 6 days from the start of therapy. Exactly the same drugs and doses were used.

At the time of treatment initiation, 10/11 had fever and received nasal oxygen therapy. Within 5 days, one patient died, two were transferred to the ICU. In one patient, hydroxychloroquine and azithromycin were discontinued after 4 days because of a prolongation of the QT interval from 405 ms before treatment to 460 and 470 ms under the combination. Mean through blood concentration of hydroxychloroquine was 678 ng/mL (range: 381-891) at days 3-7 after treatment initiation.
Repeated nasopharyngeal swabs in 10 patients (not done in the patient who died) using a qualitative PCR assay.. were still positive for SARS-CoV2 RNA in 8/10 patients (80%, 95% confidence interval: 49-94) at days 5 to 6 after treatment initiation.

Keep in mind that in the early study 12% of non-treated patients cleared their virus. Here 20% of treated cleared and 80% failed.

The authors' conclusion:
In summary, despite a reported antiviral activity of chloroquine against COVID-19 in vitro, we found no evidence of a strong antiviral activity or clinical benefit of the combination of hydroxychloroquine and azithromycin for the treatment of our hospitalized patients with severe COVID-19.

This is how science works. Someone tests a hypothesis and makes their results public. Others then attempt to replicate those findings. After enough different scientists have tested the suggestion a consensus will be reached if the data holds up to scrutiny. It is too early to know which way this is going to go, but 100% efficacy as was claimed now seems in doubt, unfortunately.

Also note that 1 of 11 had to have the medication stopped because of unexpected cardiac changes putting him or her at risk for sudden death after just a few doses. These medications are not without risk.

[chet2020]

Good review, thank you.

[manaboutown]

The COVID-19 Pandemic: Brand New Research on Hydroxychloroquine Shows More Positive Signs It Could Be a Treatment for COVID-19 | The Dr. Oz Show (https://www.doctoroz.com/episode/covid-19-pandemic-brand-new-research-hydroxychloroquine-shows-more-positive-signs-it-could)

[graciegirl]

Eleven patients does not make for a large study to prove or disprove anything and I am sure that is the point you are making.

We all are clutching at straws. Hoping for a vaccine sooner than predicted. Stay safe, Doctor. I like to debate you on politics but highly respect your medical experience and knowledge.

[skyking]

I like Dr Oz.

I assume if BlueAsh gets the virus he will refuse the Hydroxychloroquine.

If I get it I will welcome anything that won't kill me.

[blueash]

And today a new study. This out of China so some of you don't believe anything out of China can ignore this one, unless of course it fits your preconceived ideas.

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial | medRxiv (https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2)

This study was randomized with a control group (https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2.full.pdf). It has not been peer reviewed. It was done on patients with mild disease, not severe disease.

But for Time to clinical recovery, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 32) compared with the control group (54.8%, 17 of 32). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group

All the patients received what the article calls standard therapy

all received the standard treatment (oxygen therapy, antiviral agents, antibacterial agents, and immunoglobulin, with or without corticosteroids), patients in the HCQ treatment group received additional oral HCQ (hydroxychloroquine sulfate tablets, Shanghai Pharma) 400 mg/d (200 mg/bid) between days 1 and 5

So this is not a study of HCQ, rather it is a study of HCQ given with antivirals, antibacterials, immunoglobin, and sometimes steroids. Keep the findings clear in your mind that therefore this study does not show that HCQ by itself benefits. Only that HCQ when added to all those other interventions shows benefit.

Also note that the only statistically significant benefit was in time to decrease fever and cough. The difference in chest findings tended to favor HCQ but was not statistically significant.

As to the personal attacks at me for actually posting the studies and their findings. I have posted every single one I have found, both those that show benefit and those that failed. It is about 50/50 at this time. It you already have your mind made up you have my permission to stop reading my posts about the studies. I don't have my mind made up because the data is not clear and the science is not established. Some people have open and inquisitive minds and are amenable to change based on evidence. Some people don't.

[blueash]

Eleven patients does not make for a large study to prove or disprove anything and I am sure that is the point you are making.

We all are clutching at straws. Hoping for a vaccine sooner than predicted. Stay safe, Doctor. I like to debate you on politics but highly respect your medical experience and knowledge.

Exactly correct. This is a small study that attempted to replicate a very specific finding from another study.. That HCQ and Zithromax combined was 100% effective in making patients culture/PCR negative. This study failed to replicate that finding and in fact failed to show any benefit at reducing that specific goal, making the patient virus negative.

And as you are a reliable reader I'll digress here to explain culture vs. PCR. In the cultures done in the French studies, a sample is taken then incubated with live cells. If there is virus present those cells are disrupted and this alteration is visually confirmed by microscope. In pcr testing the presence of the RNA [like DNA] known to exist in the virus is measured. PCR is what the labs are using in large scale testing. This distinction is potentially important. A viral culture proves that the virus is still active and capable of attacking cells. While a virus is not "alive" that is a reasonable analogy. On the other hand, a positive PCR could occur if inactive viral particles are present which still have RNA intact but are no longer capable of causing disease. There are animal and human studies showing that the PCR stays positive after the culture becomes negative in other corona virus diseases. You can read about them in the Lancet (https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30237-1/fulltext)

In a ferret model of H1N1 infection, the loss of viral culture positivity but not the absence of viral RNA coincided with the end of the infectious period. In fact, real-time reverse transcriptase PCR results remained positive 6–8 days after the loss of transmissibility. For SARS coronavirus, viral RNA is detectable in the respiratory secretions and stools of some patients after onset of illness for more than 1 month, but live virus could not be detected by culture after week 3

But because viral cultures are very difficult to do, using PCR is standard. You have certainly read reports of Covid being found in stool samples after clinical recovery. Those are AFAIK all PCR findings.

[bumpygreens]

blueish, thanks for the posts. Ignore the personal attacks. We already know the outcome of assuming.

[blueash]

blueish, thanks for the posts. Ignore the personal attacks. We already know the outcome of assuming.

Sure enough. Mrs Blueash asks what I'm doing on the laptop. I just tell her "pie fights"

[skyking]

Hydroxychloroquine 'most effective' coronavirus treatment: poll (https://nypost.com/2020/04/02/hydroxychloroquine-most-effective-coronavirus-treatment-poll/)

[CFrance]

There have been many threads pushing hydroxychloroquine with and without azithromycin. This combination has been touted by many here and by some elsewhere as having been proven. I have participated in the TOTV threads cautioning that the data are not clear and more studies are being done.

One is now ready for publication (https://pdf.sciencedirectassets.com/272288/AIP/1-s2.0-S0399077X20300858/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjECkaCXVzLWVhc3QtMSJHMEUCIQDR DvWeUwiwp%2F6SpknE6xlD5iSILxS%2BfsYVa08Ty4xwOwIgCB NaYgYB8i2L80b%2BdcAtn8fRIa6GKmxtMADcDL7wJ8sqtAMIMh ACGgwwNTkwMDM1NDY4NjUiDEya8bjpVeLE1F9nQiqRA9muxOqg Gz%2BDnVG9JxdCgzPvmgmlFBd6YjrIZwxleD%2BVD89JIfiyrT rP7X5e2h%2Fk0MJ62QmqCDxuy89y1woqnNCgD5CboQ3VIsOboS DsX8Aag3JHRLnevfz6hrJR1ouTDUjckhzs1Zp48KZa7ejkU9BT jrmvyIWCdTfzz%2BUWb2vlhBtPZ6WJfJOiPyXcH3hUV0WHpaQm 0T9NNyZFVcG6%2BhpzDbwOIF7HOSTPAeit%2BEs40bRMEalSBI ReUphDdecviHWnMDVF1VNlLzqKwaPMJusWbDEMUWmxJ%2BZyKR B5J7yzGScIHXxQExVcmuRDglvcBH%2Bl5ZosGIEB8PjhlX5Xk5 ZoKpk5wiihlxfAgZzgzwyidhrejin6U8zJJAZuJh5RBnd2xf4% 2BU5hf0pAgxL75cKVzmNxVLCS9d7B1wrOZl6FuFnIjTam%2Far KRcnkQpeclw1UOZpJU7lbsNU2gFpUsmyrphbXNpqGnunMJxjnF JDWUtOClztW%2BnzV22IY4jH2njnEJf%2BoCDFTuSFJmr9oh5T CGMI%2BJk%2FQFOusBYgv3SI6TCw2d%2Bbl9Fz0YrmdRMWY%2F tY5OZlFpDSxkaKyRlWzowe%2B0ZOCMB6Gu1XMVAfVXdHDok9D3 A4auOR7%2BsXbXZWFWbpp51qq0ANAfcPfzORgul5EXMU85G0C% 2FEJvQ%2FYHcJcnYcvELAaulZ41y1b%2FSEOQFm1frjgw3W%2B %2BFLU0ucPTdAD1bKZhy%2BVSEpAO%2B247l9s64fvQSAlt%2B TWJyRxgXBTaKN9Izm%2FnOUFUTw2XO9IgPRUjApKF4lKY88mkC EvpQt1rp0qBdUSwbSHqdmKWdwOYuzUK6pAfajq9xF%2FjnprsX ChCDh%2BypUA%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200401T174718Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYVYI6JHKZ%2F20200401%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=9d5a465dd29bfe1db438bec72a086ae6e01957fc 3d590f854eba587b3a863cba&hash=63ce08950c07b11e582d87977671fea1f9a0162273453 05f1708877d0e5a0d8b&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd08 6a07176afe7c76c2c61&pii=S0399077X20300858&tid=spdf-9c42051d-9caf-4f64-82f0-29e8efd2be81&sid=d29e890e8cf6224ff108c23972ccda67b0e4gxrqa&type=client). Like the one that started it all, this is from France. It looked at 11 patients in Paris to attempt to replicate the earlier study where it was claimed that 6 of 6 patients given the combination had no virus detected after 6 days from the start of therapy. Exactly the same drugs and doses were used.



Keep in mind that in the early study 12% of non-treated patients cleared their virus. Here 20% of treated cleared and 80% failed.

The authors' conclusion:


This is how science works. Someone tests a hypothesis and makes their results public. Others then attempt to replicate those findings. After enough different scientists have tested the suggestion a consensus will be reached if the data holds up to scrutiny. It is too early to know which way this is going to go, but 100% efficacy as was claimed now seems in doubt, unfortunately.

Also note that 1 of 11 had to have the medication stopped because of unexpected cardiac changes putting him or her at risk for sudden death after just a few doses. These medications are not without risk.
Thanks for the explanation. You are my go-to poster on TOTV for matters medical.

[OrangeBlossomBaby]

Eleven patients does not make for a large study to prove or disprove anything and I am sure that is the point you are making.

We all are clutching at straws. Hoping for a vaccine sooner than predicted. Stay safe, Doctor. I like to debate you on politics but highly respect your medical experience and knowledge.

11 patients makes for an absolutely guaranteed, solid, confirmed, bonafide, verified, reliable prediction that this cocktail will -not- work 100%, AND that it comes with risk of death (since 1 had to discontinue because the drug was giving him deadly side effect).

When you start with the hypothesis that it's 100% effective, then a single failure to be effective - crumbles that hypothesis and renders it categorically false.

[skyking]

???? Where did anyone say it was 100% effective? Very few medications are.

So you are saying that it is 100% ineffective? That's a false assumption. Also the drug has been around since 1955. Any adverse effects are well known.

[B767drvr]

11 patients makes for an absolutely guaranteed, solid, confirmed, bonafide, verified, reliable prediction that this cocktail will -not- work 100%, AND that it comes with risk of death (since 1 had to discontinue because the drug was giving him deadly side effect).

When you start with the hypothesis that it's 100% effective, then a single failure to be effective - crumbles that hypothesis and renders it categorically false.

Um... not a scientist... but think you are going to eat crow.

[Villageswimmer]

Thanks for the explanation. You are my go-to poster on TOTV for matters medical.

I agree. Thank you for your professional, unbiased messages. The fact that you take the time to post shows that you care about others.

[karostay]

new class of Drs that graduated from online U

[blueash]

11 patients makes for an absolutely guaranteed, solid, confirmed, bonafide, verified, reliable prediction that this cocktail will -not- work 100%, AND that it comes with risk of death (since 1 had to discontinue because the drug was giving him deadly side effect).

When you start with the hypothesis that it's 100% effective, then a single failure to be effective - crumbles that hypothesis and renders it categorically false.

Be cautious not to over-interpret findings in either direction. The original study from Marseille did report that 100% of six patients given both hydroxychloroquine and Zithromax cleared of detectible virus, both by culture and PCR. However the author made no claim that it would work 100% on all patients. Most studies report a confidence interval or range. That is - given the result we found, what is the true result in a larger study likely to show. These authors did not calculate an interval. They just reported their data.

Think of it this way. You are going to flip a coin. We know that it should be 1/2 heads, 1/2 tails. But you are coin naïve and don't know that. So you flip it six times and get all heads. Does that prove that all coins have heads on both sides? Or that no matter what else, the head side always lands up even if there are other options? Another group tries to replicate. It tosses a coin 10 times. It gets 8 tails and 2 heads. That doesn't prove your 6 results were wrong only that your study had too few examples to establish the scientific proof to answer "What are the odds when you flip a coin". The only thing the second study did is show that any conclusion made on the first 6 coin flips was wrong as the test size was inadequate.

When you hear about meta analysis studies, those are when the work of other groups is combined to get a better picture because we have more numbers. In our coin case we can say we have 6 + 10 = 16 flips if we combine data. And our result is amazingly 8 heads and 8 tails. It doesn't usually work out that well. But even with that result it is way to early to say "coin flips will result in 1/2 heads" because clearly if the real result is 60% to 40% after only 16 flips we could easily have 1/2, 1/2. If this were a study we should report our result as 50% heads with a confidence interval.

This is a long explanation but it is important to understand why some are cautious about drawing final conclusions from small data sets. However, your statement that the second study established that use of HCZ and Zith is NOT 100% effective is accurate. It still could be 99% and give the results we have so far. It could be 0 % and give the results we have so far. How could it be 0 when there are patients who got the meds and cleared. It surely must be higher than zero!

No, because you cannot show that those patients who cleared did so because of the drug. That is why you need a control group as I have stressed. You have to show how many patients become test negative with no treatment before you can establish your intervention had an effect on the outcome

Example: If without any treatment 1/2 of Covid patients become test negative by 5 days [their body clears the virus itself] and 1/2 are still positive by 5 days then I do foot massage on 10 patients with Covid and publish my result that after only 5 days of massage 1/2 of those patients are now Covid free, my data is true but any conclusion such as Foot Massage has been shown to cure 50% of patients is false. Foot massage caused no improvement at all.

It is very difficult for people not to conclude that results must be caused by prior actions. The phrase post hoc ergo propter hoc gets thrown about in that situation. My favorite example is that you can show that having the sun warm the water at the beach causes drowning. The data are clear. As the water gets warmer more people drown. You see through that because you know there is some other factor I am not taking into consideration. But that is not clear if you don't already have knowledge about the topic and can't see the hocus pocus of the statistical manipulation.

[blueash]

Hydroxychloroquine 'most effective' coronavirus treatment: poll (https://nypost.com/2020/04/02/hydroxychloroquine-most-effective-coronavirus-treatment-poll/)

I have for you a more comprehensive poll result on the proper handling of Covid

Just a brief update on the current situation in America ......... American Medical Association has weighed in on Trump's COVID response:

The Allergists were in favor of scratching it, but the Dermatologists advised not to make any rash moves.
The Gastroenterologists had sort of a gut feeling about it, but the Neurologists thought the Administration had a lot of nerve.
Meanwhile, Obstetricians felt certain everyone was laboring under a misconception, while the Ophthalmologists considered the idea shortsighted.
Pathologists yelled, "Over my dead body!" while the Pediatricians said, "Oh, grow up!"
The Psychiatrists thought the whole idea was madness, while the Radiologists could see right through it.
Surgeons decided to wash their hands of the whole thing and the Internists claimed it would indeed be a bitter pill to swallow.
The Plastic Surgeons opined that this proposal would "put a whole new face on the matter."
The Podiatrists thought it was a step forward, but the Urologists were ****ed off at the whole idea.
Anesthesiologists thought the whole idea was a gas, and those lofty Cardiologists didn't have the heart to say no.
In the end, the Proctologists won out, leaving the entire decision up to the ******** in Washington.

[graciegirl]

I have for you a more comprehensive poll result on the proper handling of Covid

Just a brief update on the current situation in America ......... American Medical Association has weighed in on Trump's COVID response:

The Allergists were in favor of scratching it, but the Dermatologists advised not to make any rash moves.
The Gastroenterologists had sort of a gut feeling about it, but the Neurologists thought the Administration had a lot of nerve.
Meanwhile, Obstetricians felt certain everyone was laboring under a misconception, while the Ophthalmologists considered the idea shortsighted.
Pathologists yelled, "Over my dead body!" while the Pediatricians said, "Oh, grow up!"
The Psychiatrists thought the whole idea was madness, while the Radiologists could see right through it.
Surgeons decided to wash their hands of the whole thing and the Internists claimed it would indeed be a bitter pill to swallow.
The Plastic Surgeons opined that this proposal would "put a whole new face on the matter."
The Podiatrists thought it was a step forward, but the Urologists were ****ed off at the whole idea.
Anesthesiologists thought the whole idea was a gas, and those lofty Cardiologists didn't have the heart to say no.
In the end, the Proctologists won out, leaving the entire decision up to the ******** in Washington.

And the psychologists knew how they felt about it.

[chet2020]

Gov Cuomo mentioned a hydroxychloroquine treatment study at one of his press conferences. I keep looking for it on clinicaltrials.gov, but am not finding it. What I have found:

Sanofi: Hydroxychloroquine in Outpatient Adults With COVID-19 (210 patients). This tests drop in viral load in patients diagnosed with coronavirus per PCR test.

Columbia U: Hydroxychloroquine Post Exposure Prophylaxis for Coronavirus Disease (COVID-19). This study will test if hydroxychloroquine may be used to prevent the development of COVID-19 symptoms in persons who live with an individual who has been diagnosed with COVID-19.

There are other studies also, but I'm looking for a treatment study of hospitalized (seriously ill) patients with COVID-19 being run in NY. Maybe it's posted and I'm missing it. The Sanofi study is listed as "recruiting" and was just posted today, so perhaps the study I'm looking for simply has not dropped yet. Or maybe I am misinterpreting Cuomo's remarks. If anyone has any insights, I'm interested. Thank you.

[Challenger]

Sure enough. Mrs Blueash asks what I'm doing on the laptop. I just tell her "pie fights"

" and ye shall know the Truth, and the Truth shall make you free"