Anecdotal evidence is not a valid means of analyzing medical data.
Hundreds of (mostly small) clinical trials were launched in the spring of 2020 to evaluate if hydroxychloroquine could prevent or treat COVID-19. According to publicly available data, 247 such trials were registered.2 In this gold rush, some of these trials competed for the same patients including, unfortunately, trials that we collectively participated in. Regrettably, before the first randomized controlled trial was complete,3 hydroxychloroquine became a cause célèbre. It was endorsed by an array of notable (and polarizing) individuals and supported by a variety of confounded observational studies. Many providers began prescribing the drug4 and patients began to either request hydroxychloroquine or, alternatively, to fear it due to the ensuing public pushback against the public promotion of this unproven treatment and a high-profile article which was subsequently retracted.5 Consequently, most outpatient trials failed to enroll to completion, and none were independently large enough to definitively refute a small benefit in this setting.
Against this backdrop, the publication in this issue of The Lancet Regional Health – Americas of a large, double-blind randomized controlled trial of hydroxychloroquine in 1372 participants with initially mild COVID-19 conducted by the COPE-COALITION V group is noteworthy and laudable.6 Although this well-designed and conducted trial fell short of its recruitment goal of 1620 infected participants – stymied by the high rate of enrolled participants in whom the infection could not be confirmed by PCR or serology – it is the largest outpatient therapeutic trial of hydroxychloroquine published to date. Like dozens of smaller trials published before, it failed to demonstrate any benefit to hydroxychloroquine in preventing progression of COVID-19 among outpatients with initially mild COVID-19.
Interesting that you should post this link to the Lancet study. It is actually Dr. Boulware to whom I referred about not disclosing his conflicts of interest.
From what I recall, the dosing was off - and not given with Zinc and Azithromycin. Zinc and the Z-pack inhibit viral replication; HCQ is what I see referred to as a 'zinc ionophore', allowing zinc into the cell to hinder viral replication. This is the protocol that every doctor I read advocate - the three in conjunction, EARLY in the viral stages. The dosing in the Boulware study was also well north of what the advocating doctors recommended, which is what triggered the adverse reactions.
In fact, the NIH treatment guidelines used to include this information in their treatment guidelines. Knowing how uncomfortable information can sometimes disappear from government websites, I downloaded the PDF, and this is copied from an earlier version. Just as I suspected, the section on HCQ has been completely removed.
"Chloroquine is an antimalarial drug that was developed in 1934. Hydroxychloroquine, an analogue of chloroquine, was developed in 1946. Hydroxychloroquine is used to treat autoimmune diseases, such as
systemic lupus erythematosus and rheumatoid arthritis, in addition to malaria.
Both chloroquine and hydroxychloroquine increase the endosomal pH, which inhibits fusion between SARS-CoV-2 and the host cell membrane.1 Chloroquine inhibits glycosylation of the cellular
angiotensin-converting enzyme 2 (ACE2) receptor, which may interfere with the binding of SARS-CoV to the cell receptor.2 In vitro studies have suggested that both chloroquine and hydroxychloroquine may block the transport of SARS-CoV-2 from early endosomes to endolysosomes, possibly preventing the
release of the viral genome.3 Both chloroquine and hydroxychloroquine also have immunomodulatory effects, which have been hypothesized to be another potential mechanism of action for the treatment of COVID-19. Azithromycin has antiviral and anti-inflammatory properties. When used in combination with hydroxychloroquine, it has been shown to have a synergistic effect on SARS-CoV-2 in vitro and in molecular modeling studies.4,5 However, despite demonstrating antiviral activity in some in vitro systems, neither hydroxychloroquine plus azithromycin nor hydroxychloroquine alone reduced upper or lower respiratory tract viral loads or demonstrated clinical efficacy in a rhesus macaque model.6
The safety and efficacy of chloroquine or hydroxychloroquine with or without azithromycin and
azithromycin alone have been evaluated in randomized clinical trials, observational studies, and/or
single-arm studies. Please see Table 2b for more information.
Recommendation
• The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of chloroquine or hydroxychloroquine and/or azithromycin for the treatment of COVID-19 in hospitalized patients (AI) and in nonhospitalized patients (AIIa).
So my main beef is that in the year before the 'vaccines' were introduced, which we now know did not prevent infection nor transmission of the Covid virus, this drug, when used in combination with Zinc and a Z-pak was discarded, even though they could have worked, because they didn't get the results they wanted in Rhesus Macaque monkeys. Unconscionable decision.
The information about the early recommendations recommending hydroxychlorquine is not hidden. Other studies found no benefit of hydroxychloroquine on COVID
The RECOVERY Trial from the University of Oxford is a large, randomized, controlled, open-label study evaluating a number of potential treatments for patients hospitalized with COVID-19. The study is being conducted by researchers at the University of Oxford in the UK (the hydroxychloroquine arm is now halted).
In the RECOVERY Trial, investigators reported that there was no beneficial effect or reduction of death in hospitalized patients with COVID-19 receiving hydroxychloroquine.
In this study, 1561 patients received hydroxychloroquine and were compared to 3155 patients receiving standard care only. No difference was found in the primary endpoint, which was the incidence of death at 28 days (26.8% hydroxychloroquine vs. 25% usual care, 95% CI 0.96-1.23; p=0.18).
In addition, hydroxychloroquine treatment was associated with an increased length of stay in the hospital and increased need for invasive mechanical ventilation.
Based on this data, investigators stopped enrollment in the RECOVERY hydroxychloroquine arm on June 5th, 2020.
In a multicenter, randomized, open-label, controlled trial published in July 2020 by Cavalcanti and colleagues in the New England Journal of Medicine (NEJM), hydroxychloroquine use was studied in patients who were hospitalized with mild-to-moderate COVID-19.
Patients received hydroxychloroquine (400 mg twice daily for 7 days), hydroxychloroquine with azithromycin (hydroxychloroquine 400 mg twice daily + azithromycin 500 mg once daily for 7 days), or standard care only.
The clinical status of these patients at day 15 was not improved as compared with the patients receiving only standard care.
In addition, researchers noted that prolonged QT intervals (which may lead to abnormal heart rates and death) and elevated liver enzymes were higher in patients receiving hydroxychloroquine, either with or without azithromycin.
A randomized, double-blind, placebo-controlled trial from Skipper and colleagues was conducted in 423 outpatients (not in the hospital) with early COVID-19. It was published in the Annals of Internal Medicine in July 2020.
Patients received oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or a placebo (inactive treatment).
Researchers found that over a 14 day period a change in symptom severity and the percent of patients with ongoing symptoms did not differ significantly between groups, signaling no effect from the hydroxychloroquine treatment.
However, side effects were significantly greater in the group receiving hydroxychloroquine compared to placebo (43% hydroxychloroquine versus 22% placebo (P < 0.001). Rates of hospitalizations and deaths did not differ significantly.
Hydroxychloroquine has no clinical benefit and has problematic side effects. I cannot change your mind. I offer data that supports the vaccines over hydroxychloroquine in preventing serious disease or hospitalization. You reject the other data. Life goes on.
I recently saw a clip of Bill Maher discussing vaccines with Roseanne Barr. I asked myself why would I believe anything these entertainers offered regarding my health. I do pay attention when a well known pediatric immunologist like Paul Offitt questions if low risk people should still be recommended to have COVID vaccination at this stage of the disease.
Nor can I change your mind. You have not yet cited a study that followed the published protocols for HCQ use. The Zelenko protocol and that posted by the FLCCC used consistent 400mg daily (200 mg given twice daily) for 5-10 days, with zinc (they recommend 75-100mg per day). For those hospitalized, they also recommend prednisone, something that I have taken for respiratory issues several times outpatient prior to Covid, but which, for whatever reason the medical 'experts' decided was too dangerous to prescribe for outpatient use with Covid. From what I have read, it was the high dosage of HCQ that caused the problematic side effects. The Skipper study was particularly highly dosed. Day one is 3.5 times the daily recommended dose of HCQ for FLCCC protocol. Days 2-5 is 1.5 times the recommended dose. These studies are not even comparable to what Zelenko and FLCCC recommended. The one thing that I learned, and I will fully acknowledge that I am no scientist, is that a RCT can be skewed to deliver whatever result the sponsor want. Let's see a RCT that follows to a T the protocols that I have noted and let's see what happens. Your Substack bio simply indicates that you are a 'writer'. I don't see anything that qualifies you as more enlightened than I. I will also fully admit that I don't know what the truth is, but I would like to know, and I don't see how we get there without honest RCT's. You mentioned once that 'anecdotal evidence is not a valid means of analyzing medical data'. I would argue that RCT's are precisely that - a collection of anecdotal evidence. The problem is that we cannot ever reach a consensus if every RCT uses different methodologies and protocols and circumstances. I see your point of view; I just can't see why you can't acknowledge that the RCT data that you presented is not even close to representing a test of what Dr. Zelenko and the FLCCC recommended for early treatment.
It’s there. It just is not given the press that the studies you cited have. Unfortunately most people look no further than the study’s conclusions to see what exactly the study entailed. What type of patient was included? What exactly were the control patients given? What protocol - dosing, duration, etc? What other studies were done involving this medication given to treat this disease at the same stage of illness, and what did they show? The number of studies done is pointless unless they are all conducted the same way on the same type of patient set using the same pharmaceutical in the same dose.studies show that aspirin is safe, but only if the recommended dosage is followed.
When the J&J vaccine was associated with clots, the trial was stopped pending analysis. Science changes as new data pours in. Recommendations change. The HCQ folks are stuck in time.
Anecdotal evidence is not a valid means of analyzing medical data.
Hundreds of (mostly small) clinical trials were launched in the spring of 2020 to evaluate if hydroxychloroquine could prevent or treat COVID-19. According to publicly available data, 247 such trials were registered.2 In this gold rush, some of these trials competed for the same patients including, unfortunately, trials that we collectively participated in. Regrettably, before the first randomized controlled trial was complete,3 hydroxychloroquine became a cause célèbre. It was endorsed by an array of notable (and polarizing) individuals and supported by a variety of confounded observational studies. Many providers began prescribing the drug4 and patients began to either request hydroxychloroquine or, alternatively, to fear it due to the ensuing public pushback against the public promotion of this unproven treatment and a high-profile article which was subsequently retracted.5 Consequently, most outpatient trials failed to enroll to completion, and none were independently large enough to definitively refute a small benefit in this setting.
Against this backdrop, the publication in this issue of The Lancet Regional Health – Americas of a large, double-blind randomized controlled trial of hydroxychloroquine in 1372 participants with initially mild COVID-19 conducted by the COPE-COALITION V group is noteworthy and laudable.6 Although this well-designed and conducted trial fell short of its recruitment goal of 1620 infected participants – stymied by the high rate of enrolled participants in whom the infection could not be confirmed by PCR or serology – it is the largest outpatient therapeutic trial of hydroxychloroquine published to date. Like dozens of smaller trials published before, it failed to demonstrate any benefit to hydroxychloroquine in preventing progression of COVID-19 among outpatients with initially mild COVID-19.
https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(22)00085-0/fulltext
I don’t find it remarkable that those who faile hydroxychloroquine did not show up in droves.
Interesting that you should post this link to the Lancet study. It is actually Dr. Boulware to whom I referred about not disclosing his conflicts of interest.
https://revivethera.com/2020/03/revive-therapeutics-appoints-dr-david-boulware-md-as-scientific-advisor-for-infectious-diseases-including-covid-19/
From what I recall, the dosing was off - and not given with Zinc and Azithromycin. Zinc and the Z-pack inhibit viral replication; HCQ is what I see referred to as a 'zinc ionophore', allowing zinc into the cell to hinder viral replication. This is the protocol that every doctor I read advocate - the three in conjunction, EARLY in the viral stages. The dosing in the Boulware study was also well north of what the advocating doctors recommended, which is what triggered the adverse reactions.
In fact, the NIH treatment guidelines used to include this information in their treatment guidelines. Knowing how uncomfortable information can sometimes disappear from government websites, I downloaded the PDF, and this is copied from an earlier version. Just as I suspected, the section on HCQ has been completely removed.
"Chloroquine is an antimalarial drug that was developed in 1934. Hydroxychloroquine, an analogue of chloroquine, was developed in 1946. Hydroxychloroquine is used to treat autoimmune diseases, such as
systemic lupus erythematosus and rheumatoid arthritis, in addition to malaria.
Both chloroquine and hydroxychloroquine increase the endosomal pH, which inhibits fusion between SARS-CoV-2 and the host cell membrane.1 Chloroquine inhibits glycosylation of the cellular
angiotensin-converting enzyme 2 (ACE2) receptor, which may interfere with the binding of SARS-CoV to the cell receptor.2 In vitro studies have suggested that both chloroquine and hydroxychloroquine may block the transport of SARS-CoV-2 from early endosomes to endolysosomes, possibly preventing the
release of the viral genome.3 Both chloroquine and hydroxychloroquine also have immunomodulatory effects, which have been hypothesized to be another potential mechanism of action for the treatment of COVID-19. Azithromycin has antiviral and anti-inflammatory properties. When used in combination with hydroxychloroquine, it has been shown to have a synergistic effect on SARS-CoV-2 in vitro and in molecular modeling studies.4,5 However, despite demonstrating antiviral activity in some in vitro systems, neither hydroxychloroquine plus azithromycin nor hydroxychloroquine alone reduced upper or lower respiratory tract viral loads or demonstrated clinical efficacy in a rhesus macaque model.6
The safety and efficacy of chloroquine or hydroxychloroquine with or without azithromycin and
azithromycin alone have been evaluated in randomized clinical trials, observational studies, and/or
single-arm studies. Please see Table 2b for more information.
Recommendation
• The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of chloroquine or hydroxychloroquine and/or azithromycin for the treatment of COVID-19 in hospitalized patients (AI) and in nonhospitalized patients (AIIa).
So my main beef is that in the year before the 'vaccines' were introduced, which we now know did not prevent infection nor transmission of the Covid virus, this drug, when used in combination with Zinc and a Z-pak was discarded, even though they could have worked, because they didn't get the results they wanted in Rhesus Macaque monkeys. Unconscionable decision.
The information about the early recommendations recommending hydroxychlorquine is not hidden. Other studies found no benefit of hydroxychloroquine on COVID
The RECOVERY Trial from the University of Oxford is a large, randomized, controlled, open-label study evaluating a number of potential treatments for patients hospitalized with COVID-19. The study is being conducted by researchers at the University of Oxford in the UK (the hydroxychloroquine arm is now halted).
In the RECOVERY Trial, investigators reported that there was no beneficial effect or reduction of death in hospitalized patients with COVID-19 receiving hydroxychloroquine.
In this study, 1561 patients received hydroxychloroquine and were compared to 3155 patients receiving standard care only. No difference was found in the primary endpoint, which was the incidence of death at 28 days (26.8% hydroxychloroquine vs. 25% usual care, 95% CI 0.96-1.23; p=0.18).
In addition, hydroxychloroquine treatment was associated with an increased length of stay in the hospital and increased need for invasive mechanical ventilation.
Based on this data, investigators stopped enrollment in the RECOVERY hydroxychloroquine arm on June 5th, 2020.
In a multicenter, randomized, open-label, controlled trial published in July 2020 by Cavalcanti and colleagues in the New England Journal of Medicine (NEJM), hydroxychloroquine use was studied in patients who were hospitalized with mild-to-moderate COVID-19.
Patients received hydroxychloroquine (400 mg twice daily for 7 days), hydroxychloroquine with azithromycin (hydroxychloroquine 400 mg twice daily + azithromycin 500 mg once daily for 7 days), or standard care only.
The clinical status of these patients at day 15 was not improved as compared with the patients receiving only standard care.
In addition, researchers noted that prolonged QT intervals (which may lead to abnormal heart rates and death) and elevated liver enzymes were higher in patients receiving hydroxychloroquine, either with or without azithromycin.
A randomized, double-blind, placebo-controlled trial from Skipper and colleagues was conducted in 423 outpatients (not in the hospital) with early COVID-19. It was published in the Annals of Internal Medicine in July 2020.
Patients received oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or a placebo (inactive treatment).
Researchers found that over a 14 day period a change in symptom severity and the percent of patients with ongoing symptoms did not differ significantly between groups, signaling no effect from the hydroxychloroquine treatment.
However, side effects were significantly greater in the group receiving hydroxychloroquine compared to placebo (43% hydroxychloroquine versus 22% placebo (P < 0.001). Rates of hospitalizations and deaths did not differ significantly.
https://www.drugs.com/medical-answers/hydroxychloroquine-effective-covid-19-3536024/#:~:text=In%20this%20study%2C%201561%20patients,1.23%3B%20p%3D0.18).
Hydroxychloroquine has no clinical benefit and has problematic side effects. I cannot change your mind. I offer data that supports the vaccines over hydroxychloroquine in preventing serious disease or hospitalization. You reject the other data. Life goes on.
I recently saw a clip of Bill Maher discussing vaccines with Roseanne Barr. I asked myself why would I believe anything these entertainers offered regarding my health. I do pay attention when a well known pediatric immunologist like Paul Offitt questions if low risk people should still be recommended to have COVID vaccination at this stage of the disease.
Nor can I change your mind. You have not yet cited a study that followed the published protocols for HCQ use. The Zelenko protocol and that posted by the FLCCC used consistent 400mg daily (200 mg given twice daily) for 5-10 days, with zinc (they recommend 75-100mg per day). For those hospitalized, they also recommend prednisone, something that I have taken for respiratory issues several times outpatient prior to Covid, but which, for whatever reason the medical 'experts' decided was too dangerous to prescribe for outpatient use with Covid. From what I have read, it was the high dosage of HCQ that caused the problematic side effects. The Skipper study was particularly highly dosed. Day one is 3.5 times the daily recommended dose of HCQ for FLCCC protocol. Days 2-5 is 1.5 times the recommended dose. These studies are not even comparable to what Zelenko and FLCCC recommended. The one thing that I learned, and I will fully acknowledge that I am no scientist, is that a RCT can be skewed to deliver whatever result the sponsor want. Let's see a RCT that follows to a T the protocols that I have noted and let's see what happens. Your Substack bio simply indicates that you are a 'writer'. I don't see anything that qualifies you as more enlightened than I. I will also fully admit that I don't know what the truth is, but I would like to know, and I don't see how we get there without honest RCT's. You mentioned once that 'anecdotal evidence is not a valid means of analyzing medical data'. I would argue that RCT's are precisely that - a collection of anecdotal evidence. The problem is that we cannot ever reach a consensus if every RCT uses different methodologies and protocols and circumstances. I see your point of view; I just can't see why you can't acknowledge that the RCT data that you presented is not even close to representing a test of what Dr. Zelenko and the FLCCC recommended for early treatment.
I acknowledge the absence of data supportive of wasting resources on HCQ.
It’s there. It just is not given the press that the studies you cited have. Unfortunately most people look no further than the study’s conclusions to see what exactly the study entailed. What type of patient was included? What exactly were the control patients given? What protocol - dosing, duration, etc? What other studies were done involving this medication given to treat this disease at the same stage of illness, and what did they show? The number of studies done is pointless unless they are all conducted the same way on the same type of patient set using the same pharmaceutical in the same dose.studies show that aspirin is safe, but only if the recommended dosage is followed.
HCQ was given the same chance as other drugs. It failed. Time moves on.
Edit to add:
There was data that the vaccine prevented transmission of the early variant. When the data changed with later variants, the message changed.
https://www.reuters.com/article/idUSL1N31F20E/
When the J&J vaccine was associated with clots, the trial was stopped pending analysis. Science changes as new data pours in. Recommendations change. The HCQ folks are stuck in time.