Hydroxychloroquine beats remdesivir in drug fight against Covid-19!!
#91
09 March 2020

Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


Source: https://www.ncbi.nlm.nih.gov/pmc/article...iaa237.pdf

Quote: Abstract

Background: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

Methods: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile.

Results: Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

Conclusions: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

Surprised
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#92
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.
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#93
23-5-2020 10:25 AM
sudoku said:
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.

Hydroxychloroquine does both. Remdesivir can prevent?

Cool
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#94
23-5-2020 10:30 AM
FaTa said:
Hydroxychloroquine does both. Remdesivir can prevent?

Cool

Former have higher mortality rate in treatment. Trump using as prevention.

Latter expedite recovery.

Vaccine still to be approved.
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#95
Source: https://www.jstage.jst.go.jp/article/ddt...5/_article

Drug Discoveries & Therapeutics

Rapid Review for the Anti-Coronavirus Effect of Remdesivir

Published: April 30, 2020
Received: March 06, 2020
Released: May 06, 2020
Accepted: April 28, 2020
[Advance Publication] Released: -
Revised: April 28, 2020

Quote:3. SARS-CoV-2
Wang et al. conducted an experiment to evaluate the anti-SARS-CoV-2 effect of remdesivir (10). In time-of-addition assay using Vero E6 cells, remdesivir was found to be effective when administered 2 hours after infection at a multiplicity of infection (MOI) of 0.05. However, no prophylactic effect was observed when remdesivir was administered prior to the SARS-CoV-2 infection. The concentration for 90% of maximal effect (EC90) value of remdesivir against SARS-CoV-2 was found to be 1.76 μM. This study also revealed that remdesivir could inhibit SARS-CoV-2 infection in human liver cancer Huh-7 cells.The recent case report recorded.

The current evidence on experimental studies and clinical observation indicated that remdesivir has the potential for treating COVID-19. Nevertheless, findings from the compassionate-use study were not adequately powered with a randomized controlled design to assess the safety and efficacy of remdisivir in patients with severe COVID-19. Therefore, more evidence from randomized clinical trials (RCTs) of high quality is eventually needed to confirm its safety and efficacy.

Two phase III clinical trials had been launched in Hubei and Beijing in China in early February 2020, aiming to evaluate the safety and efficacy of remdesivir for adult patients with COVID-19 and with mild-moderate (NCT04252664, sample size: 308) and severe (NCT04257656, sample size: 452) symptoms. Subsequently, other five RCTs with similar objectives were further registered on clinicaltrials.gov. However, as of 28th April 2020, there has not been published results available in the literature. Therefore, it remains largely unknown currently regarding the benefit-harm profile of remdesivir for COVID-19.

In brief, remdesivir has been found to inhibit coronavirus and improve pulmonary functions prophylactically and therapeutically (in early stage of infection) based on evidence from both in vitro and in vivo experiments. However, evidence in patients with COVID-19 remained limited and sparse. The ongoing clinical trials will provide more high-quality evidence on the benefit-harm effect of remdesivir. Nevertheless, there are several issues of concern regarding their protocols. First, the inclusion/exclusion criteria and the outcome measurements do not include chest radiography that is one of the key elements for disease diagnosis and criteria for recovery according to Guidelines for the Diagnosis and Treatment of Novel Coronavirus (SARS-CoV-2) Infection by the National Health Commission (Trial Version 5) published by National Health and Health Commission of the people's Republic of China (13). Thus, it may incur selection and reporting bias to weaken the results. Secondly, based on the previous experiments on SARS-CoV, remdesivir was effective only when it was administered at the early stage of infection (before the initiation of the immunopathological phase of pneumonia) (8). By contrast, another study showed that remdesivir was found to be functional for SARS-CoV-2 when administered 2 hours after infection (10). These results indicated the benefit of remdesivir may heavily depend on the time of administration. No predefined plans of trial designs or statistical analyses are given in their protocols related to the optimum time of administration. Thirdly, the current evidence was insufficient to support the safety of remdesivir in humans. Even though some cytotoxicity tests suggested that remdesivir could be effective at a relatively low micromolar concentration compared with its cytotoxic concentration (8,9), the safety test in humans is still ongoing currently. Moreover, a previous randomized controlled trial reported that in patients with Ebola virus disease, the overall mortality was even higher in remdesivir group (53%) than the control group (a triple monoclonal antibody agent; 50%), although without significance (14). Therefore, extreme cautions and monitoring should be taken in the ongoing trials for COVID-19 given the safety of remdesivir remains largely unconfirmed and unknown.

To summarize, even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification. Similar to the inconclusive effect on SARS-CoV and MERS-CoV, the impact of remdesivir on the SARS-CoV-2 outbreak should not be overestimated in the current clinical practice. Further explorations remain urgently needed to treat the COVID-19 and bring the SARS-CoV-2 under control.
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#96
Trump is not an idiot, fortunately or unfortunately, depends on whether you like him or not.
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#97
23-5-2020 10:35 AM
sudoku said:
Former have higher mortality rate in treatment. Trump using as prevention.

Latter expedite recovery.

Vaccine still to be approved.

[Image: uUeXr7B.jpg]

As far as I know, the baseline used in the study are severely ill patients which is flawed & not honest at all. It was designed to fail and discredit hydroxychloroquine.

Hydroxychloroquine's usefulness is not in the late stage but early stage of infection.
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#98
23-5-2020 10:25 AM
sudoku said:
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.

Unlike hydroxychloroquine (which can prevent and recover), remdesivir is not able to prevent according to this review.

https://www.jstage.jst.go.jp/article/ddt...5/_article
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#99
Quote:[7 May 2020]
https://aapsonline.org/a-tale-of-two-dru...al-wisdom/

A Tale of Two Drugs: Money vs. Medical Wisdom
By Elizabeth Lee Vliet, M.D. – https://vivelifecenter.com/

At the Presidential Briefing on Apr 30, Dr. Anthony Fauci announced early results, prior to peer-review, of one clinical trial using remdesivir, an intravenous (IV) experimental antiviral medicine in patients hospitalized with COVID-19. At the “warp speed” currently in vogue for the Fauci-led push to a new vaccine, the very next day the FDA issued an Emergency Use Authorization (EAU) for remdesivir to be used in seriously ill hospitalized patients. To announce the emergency approval, President Trump met with the CEO of the drug’s manufacturer, Gilead Sciences, in the Oval Office.

Such rapid authorization is quite unusual with the FDA. Unlike the experimental remdesivir with no prior FDA approval, hydroxychloroquine (HCQ) required two months from reports of successful use in China and South Korea to get the Mar 28 FDA EUA for use in hospitalized COVID-19 patients. HCQ was approved in 1955 for malaria, and later for lupus and rheumatoid arthritis. Over the last 65 years, hundreds of millions of prescriptions have been written for HCQ worldwide.

The EUA for HCQ did not, however, expand its availability but imposed restrictions to prevent non-hospitalized patients from accessing the government’s stockpile of the drug. Democrat Governors Cuomo (NY), Sisolak (NV), and Whitmer (MI), then imposed restrictive orders on outpatient use, and all but four states have followed their lead.

In decades of widespread use, HCQ has an impressive safety record. Irregular heart rhythm or damage to the retina occur rarely, usually with high doses used long term. FDA shows only 62 cardiac deaths attributed to HCQ out of more than 50 million prescriptions, or 0.000124 percent (1.2 out of each 1 million Rx). Rheumatology guidelines for lupus and rheumatoid arthritis do not even require baseline electrocardiograms before prescribing HCQ, since the risk is minimal.

Approximately $70 million in U.S. taxpayer funding began Gilead’s partnership with the U.S. Army, Centers for Disease Control and Prevention (CDC), and National Institutes of Health (NIH) to develop remdesivir. Initially for treating Ebola, it failed to show benefit and was shelved. If remdesivir is used to treat COVID-19, Gilead shareholders, not the taxpayers, will profit.

Early results of the first clinical trial of remdesivir against placebo in coronavirus were announced at the White House Apr 30, and showed modest benefits, according to The New York Times. Surviving patients given remdesivir were discharged 4 days sooner than patients given placebo, though no criteria were given for determining improvement. Death rates were not significantly different. About 25 percent of patients receiving remdesivir had potentially severe side effects, including multiple organ dysfunction, septic shock, acute kidney injury, and low blood pressure. Another 23% showed evidence on lab tests of liver damage.

Gilead’s own press release revealed the side effect of acute respiratory failure in 6 percent of patients in the remdesivir 5-day treatment group, and 10.7 percent of patients in the 10-day treatment group, clearly ominous findings with a drug designed to treat respiratory failure caused by COVID-19.

Dr. Steven Nissen, Cleveland Clinic cardiologist who has conducted dozens of clinical trials, explained to The New York Times: “The disclosure of trial results in a political setting, before peer review or publication, is very unusual. Scientists will need to see figures on harms associated with the drug in order to assess its benefits…. This is too important to be handled in such a sloppy fashion.”

Dr. Michele Barry, a global health expert at Stanford University, expressed concern about Dr. Fauci’s overly enthusiastic praise for remdesivir: “It is unusual to call a drug the ‘standard of care’ until peer review of data and publication, and before studies have shown benefit in mortality.”

The leading communicable disease specialist in France, Professor Didier Raoult, asked about another odd aspect of the remdesivir trial: “Could Anthony Fauci explain why the investigators of the NIAID remdesivir trial did change the primary outcome during the course of the project?” Death as the primary outcome was moved to a secondary outcome, and days to recovery became the primary trial outcome. Changing the primary outcome before trial results are completed is highly unusual and suggests “p-hacking”—manipulating the data to get a statistically significant “p value.

In contrast, the multi-country compilation of evidence on HCQ and azithromycin in treatment of COVID-19 (updated Apr 27, 2020) has consistently shown that these older medicines prevent infections, significantly reduce severity of illness, reduce viral load and duration of infectivity, reduce number of hospitalizations, reduce ventilator use, and markedly reduce deaths. The data is far beyond “anecodotal,” as Dr. Fauci dismissively called it.

Money appears to be trumping medical wisdom in the recent enthusiasm for remdesivir based on just one study with modest results. One naturally wonders whether this may have anything to do with the fact that the “world’s largest asset manager,” BlackRock, owns the largest share of all Gilead stock at 8.4%. BlackRock’s influence in Washington, D.C., is legendary, and it recently was awarded the financial crown jewel of administering the Federal Reserve’s $4.5 Trillion COVID-19 loan bail-out program.

Is someone stacking the deck in Gilead’s favor? Nine of the experts on the NIH COVID-19 Panel recommending treatment options have disclosed financial support from Gilead. Why did these nine experts not recuse themselves? Did financial conflicts of interest affect the recommendation against HCQ, the older, safer, cheaper medicine, and for use of remdesivir, the new, expensive experimental medicine, based on weak, not-yet-peer-reviewed evidence?

HCQ has been off patent for decades, is available from a dozen U.S. generic manufacturers, and is also produced in China, India, Israel, and other countries. HCQ costs the patient on average less than $10 (range 37-63 cents per tablet), for the usual 5-7 day course of treatment. Remdesivir costs upwards of $1,000 per dose, plus the added costs of having to be hospitalized to receive it.

In addition to HCQ’s low cost, major pharmaceutical companies (Novartis, Bayer, Teva, and others) have donated nearly 50 million doses to the Strategic National Stockpile. Tragically for Americans sick with COVID-19, most of this medicine still sits in warehouses because state governments are interfering with its use in outpatients when it has greatest effect.

Patients’ lives are being sacrificed on the altar of financial interests and elite D.C. powerbrokers instead of being entrusted to the judgment of patients’ own physicians. We are witnessing the deadly consequences of bureaucrats and governors practicing medicine.

Money over medical wisdom, and politics above patients: two viruses more lethal than COVID-19.
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Reject the vaccine.

There is already a far more effective, far more safer and cheaper treatment than any vaccine or even Ebola-durg remdesivir against Covid-19......and it is available now! As a preventive and treatment, low dose hydroxycloroquine with zinc are to be administered before and during early stages and symptoms (not high-dose hydroxychloroquine only, not zinc only, not late stage or severe patients). Even if the virus mutates, this HCQ+Zinc protocol treatment is far superior against new mutations than any vaccine (which is tailored only to a specific mutation).

Quote:[28Apr2020] Hydroxychloroquine Has about 90 Percent Chance of Helping COVID-19 Patients
https://aapsonline.org/hcq-90-percent-chance/

In a letter to Gov. Doug Ducey of Arizona, the Association of American Physicians and Surgeons (AAPS) presents a frequently updated table of studies that report results of treating COVID-19 with the anti-malaria drugs chloroquine (CQ) and hydroxychloroquine (HCQ, Plaquenil®).

To date, the total number of reported patients treated with HCQ, with or without zinc and the widely used antibiotic azithromycin, is 2,333, writes AAPS, in observational data from China, France, South Korea, Algeria, and the U.S. Of these, 2,137 or 91.6 percent improved clinically. There were 63 deaths, all but 11 in a single retrospective report from the Veterans Administration where the patients were severely ill.

The antiviral properties of these drugs have been studied since 2003. Particularly when combined with zinc, they hinder viral entry into cells and inhibit replication. They may also prevent overreaction by the immune system, which causes the cytokine storm responsible for much of the damage in severe cases, explains AAPS. HCQ is often very helpful in treating autoimmune diseases such as lupus and rheumatoid arthritis.

Additional benefits shown in some studies, AAPS states, is to decrease the number of days when a patient is contagious, reduce the need for ventilators, and shorten the time to clinical recovery.


Peer-reviewed studies published from January through April 20, 2020, provide clear and convincing evidence that HCQ may be beneficial in COVID-19, especially when used early, states AAPS. Unfortunately, although it is perfectly legal to prescribe drugs for new indications not on the label, the Food and Drug Administration (FDA) has recommended that CQ and HCQ should be used for COVID-19 only in hospitalized patients in the setting of a clinical study if available. Most states are making it difficult for physicians to prescribe or pharmacists to dispense these medications.

As the letter to Gov. Ducey notes, “Many nations, including Turkey and India, are protecting medical workers and contacts of infected persons prophylactically. According to worldometers.info, deaths per million persons from COVID-19 as of Apr 27 are 167 in the U.S., 33 in Turkey, and 0.6 in India.”

After Morocco and Algeria began using HCQ, a trend break and sharp reduction in their COVID-19 case fatality rate occurred.

Vaccines and results of randomized double-blind controlled trials of new drugs are at best months away. But patients are dying now, while affordable, long-used drugs would be available except for government restrictions, AAPS states.

The Association of American Physicians and Surgeons (AAPS) has represented physicians of all specialties in all states since 1943. The AAPS motto is omnia pro aegroto, meaning everything for the patient.







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