TIME TO STOP LISTENING

I replied this on another post, yet it is also applicable here as well...

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https://www.forbes.com/sites/tarahaelle/2020/03/25/chloroquine-use-for-covid-19-shows-no-benefit-in-first-small-but-limited-controlled-trial/#13b680fc4c86
[quote]Results from the first controlled study of hydroxychloroquine for treating COVID-19 showed no significant difference in outcomes between those who received the drug and those who received usual care. Hydroxychloroquine is one of several existing drugs that scientists are hoping will show improved symptoms and recovery in clinical trials for in patients with COVID-19.

However, the study’s small size and other weaknesses mean it does not offer a lot of helpful information in determining the possible utility of hydroxychloroquine, according to experts who reviewed the study. The study also tested only hydroxychloroquine alone, not with the antibiotic azithromycin.

“The combination therapy of azithromycin and hydroxychloroquine was thought to be better over the monotherapy of hydroxychloroquine to control the mixed infection of virus and bacteria,” explained Sunit K. Singh, PhD, a professor of molecular immunology & virology and head of the molecular biology unit at Banaras Hindu University’s Institute of Medical Sciences in Varanasi, India.

Hydroxychloroquine, known by the brand name Plaquenil, is currently used to treat lupus and rheumatoid arthritis. It is slightly different from chloroquine phosphate, another drug, currently used to treat malaria, which is under investigation for treating COVID-19. Both drugs have been in use for decades but carry risks as well.

“During any outbreaks of epidemic and pandemic levels, there is hardly any time left for new drug development and clinical trials,” Dr. Singh said. Therefore clinicians will turn to trying existing drugs, known as “repurposing.”

“Many intensive care clinicians are willing to ‘try anything once’ in these unprecedented times,” said Mel Thomson, PhD, an emerging infectious disease expert and founder at VeraQ Pty Ltd in Australia, who reviewed the data. “Any widespread ‘off label’ use of anti-infective drugs, must be treated with great caution, as the unintended consequences may mean a rise in resistance to these compounds by parasites and bacteria, their original intended targets,” said Dr. Thomson, former principal investigator at Geelong Centre of Emerging infectious Diseases (GCEID) at Deakin Medical School in Geelong, Victoria Australia.

That concern, however, is more likely to relevant if hydroxychloroquine is administered along with azithromycin, as some other trials are exploring, explained Angela L. Rasmussen, PhD, a virologist in the faculty of the Center for Infection and Immunity at the Columbia Mailman School of Public Health in New York City. Because chloroquine was used so much to treat malaria throughout the 20th century, multiple species of the Plasmodium parasite that causes malaria have chloroquine resistance (which likely extends to the very similar hydroxychloroquine).

The new study, led by a team at the Shanghai Public Health Clinical Center in China, involved 30 patients hospitalized with confirmed COVID-19 between February 6-25. Half the patients were randomly assigned to receive 400 mg of hydroxychloroquine per day for 5 days on top of usual care while the other patients in the control group received usual care. A placebo was not used.

Usual care included bed rest, oxygen inhalation, and antiviral or antibiotic drugs as needed or recommended according to the hospital’s treatment plan. All patients in both groups received interferon alpha with a nebulizer, and umifenovir—an antiviral treatment approved in China for influenza—was administered to 67% of the usual care patients and 80% of the patients receiving hydroxychloroquine. Two patients received lopinavir-ritonavir, an anti-viral normally used to treat HIV infections.

At admission, the chest CT scans did not differ significantly between the two groups. No patients were pregnant or had serious underlying conditions, including neurological or psychiatric conditions.

The researchers defined their primary endpoint—the most important outcome for measuring effectiveness—as a reduction in viral load as defined by a COVID-19 test (PCR).

Here were the main findings:

One patient developed severe disease. That patient was in the hydroxychloroquine group and stopped receiving it on the fourth day. The authors state that developing severe disease did not appear related to the medication.
One week after hospitalization, 86.7% of patients in the experimental group and 93.3% of patients in the usual care group tested negative. This difference was not statistically significant.
It took 4 days for half the hydroxychloroquine patients to test negative and 2 days for half the control group to test negative. This difference was not statistically significant.
Patients’ temperatures returned to normal at approximately the same rate in both groups.
Disease progression in CT images was statistically similar between the groups (33.3% of the hydroxychloroquine group and 46.7% of the usual care group).
At two weeks, all patients in both groups tested negative and showed improvement in their symptoms.
Short-term diarrhea and abnormal liver function occurred in 26.7% of the hydroxychloroquine group and 20% of the usual care control group.
The rate of adverse events (side effects that may or may not be related to the medication) were similar in both groups.

Limitations

The study is just the first to directly compare hydroxychloroquine with a control group for treatment of COVID-19. Other studies are in progress or will begin soon.
The study is very small. The researchers estimate that a trial would require 784 patients with no drop-outs to determine whether hydroxychloroquine definitively results in better or worse outcomes.

Analysis

The authors of this new study caution against carrying out a study where all patients receive the experimental drug and compare them to historical cases because doing so can result in false positive results—a suggestion that the drug works when improvement may be due to other factors. Original optimism in hydroxychloroquine came in part from a small French trial, but it had substantial flaws, including no simultaneous control group.

But this study has major flaws as well, according to Dr. Thomson and Dr. Singh.

“This study, demonstrates the complete pointlessness of a small cohort study,” Dr. Thomson said. It has too few people in each arm, is not large enough to consider differences between men and women, does not control for antibiotics, and provides no information on secondary bacterial infections, she explained.

It would be very difficult to do a trial as large as the researchers recommend, so the authors propose that using different populations or endpoints, such as measuring a reduction in the risk of death in critically ill patients, might provide more useful information.

Another potential endpoint could be development of immunity against COVID-19, Dr. Thomson said. If no immune response is detected, patients would not have any defense against getting infected again.

While this study did not show any serious effects from hydroxychloroquine, it does have potential risks, and patients’ medical history and underlying conditions must be considered before they received it, Dr. Singh said. Still, it remains worth exploring because of anti-viral effects it has shown in other research.

“It is thought that hydroxychloroquine may have some potential effect against SARS-CoV2 because it will prevent the virus’s genetic material (RNA) from entering the part of the cell where it replicates,” Dr. Singh said. “Still we have to learn a lot about dosing of this medicine based on the severity of the disease” and other factors.
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