Three Clinical Trials Dulled Hydroxychloroquine Hope as COVID-19 Prevention and Treatment
Thu, September 29, 2022

Three Clinical Trials Dulled Hydroxychloroquine Hope as COVID-19 Prevention and Treatment



Three studies smashed the hopes of hydroxychloroquine as treatment or prevention of COVID-19. The drug was linked to either adverse effects or lack of efficacy against the disease. Still, some researchers wanted to investigate further before deciding if the drug should be removed from the equation.

The three studies that pinned hydroxychloroquine as ineffective against COVID-19 were large, randomized clinical trials conducted by different research teams. Overall, the findings of these trials highlighted the lack of clinical benefit in using the drug among COVID-19 patients. At worst, patients would be at risk of adverse effects from taking hydroxychloroquine. At best, patients would simply experience the placebo effect. Results were published in the clinical databases Recovery Trial,, and the New England Journal of Medicine.


What is the Use of Hydroxychloroquine?

Primarily, hydroxychloroquine is a medication used to treat malaria in areas where the disease remains endemic. But in areas where malaria is highly uncommon or nonexistent, the drug is used for other illnesses. As such, its application in various regions is relevant with or without malaria cases. So, when its name echoed as a COVID-19 treatment or prevention, an upset existed in the supply and demand of the medication. This affected the steady supply of hydroxychloroquine in malaria-endemic territories.

According to the American College of Rheumatology, a professional organization for rheumatologists, hydroxychloroquine is also an important medication for autoimmune disorders. The active ingredients of the drug can decrease pain and swelling associated with autoimmunity. This made the drug a potential treatment for various cases of rheumatoid arthritis, systemic lupus erythematosus, and juvenile idiopathic arthritis – arthritis in children.

Despite the known fact about the effects of hydroxychloroquine, doctors cannot specify how it interacts with the body. It is believed that the drug may be interfering with cells dedicated to immune system communication. This helps reduce the attack of immune cells on friendly cells, but the interference of hydroxychloroquine is no cure for autoimmunity.

Generally, hydroxychloroquine is well tolerated by most patients. However, uncommon and adverse effects have been documented. Some of the uncommon side effects are skin pigmentation, hair changes, and muscle weakness, while rare side effects include anemia in patients with porphyria and vision problems. Among the rare side effects, the most disturbing of late is the changes in the heart rhythm or arrhythmia. The drug can either slow the heartbeat or speed it up, and both can be fatal.



Is Hydroxychloroquine Ineffective against COVID-19?

For treating COVID-19, hydroxychloroquine is an enigma that needs to be solved. In vitro experiments showed that active ingredients can alter the cellular environment of human cells, making it harder for SARS-CoV-2 to hijack and infect them. Though, in vitro results do not always lead to similar in vivo results. Due to dynamics, in vivo results may be completely different, meaning, in labs, the drug works perfectly but inside an actual organism, the effects can be lethal.

Recently, three studies published in the same month showed that hydroxychloroquine has been observed without clinical benefit in treating COVID-19 patients. The drug has been observed as well without benefits as prevention. People who took the drug to protect themselves from the disease likely put themselves at risk of side effects, especially arrhythmia. Not only that, but they also contributed to the scarcity of hydroxychloroquine for patients with autoimmune disorders.

On June 3, 2020, a randomized clinical trial recruited 821 adults who had household or occupational exposure to COVID-19. The exposure risk was at a distance of fewer than six feet from someone with COVID-19 for over 10 minutes, without a face mask or eye shield or without a face mask only. Four days after being exposed to a carrier, participants were given either placebo or hydroxychloroquine. The doses were 800 milligrams once, followed by 600 milligrams in six to eight hours, and 600 milligrams every day for four extra days.



Results showed that out of 821 asymptomatic participants, 719 or 87.6% were found with high-risk exposure to COVID-19. Then, the incidence rate between those who were given a placebo was compared to those given hydroxychloroquine. The comparison showed no statistical difference, wherein 11.9% of those who took hydroxychloroquine and 14.3% of those who took the placebo were at risk. In terms of adverse effects, 40.1% of hydroxychloroquine participants developed side effects while only 16.8% of placebo participants developed unfavorable reactions.

On June 9, 2020, the preliminary findings of a randomized clinical trial conducted in Spain showed no remarkable differences in patients treated with hydroxychloroquine or the usual supportive care. The authors recognized the antiviral effects of the drug against SARS-CoV-2 in vitro, but the anticipated effects were not accomplished in people. The drug was simply observed ineffective as a treatment or prevention of COVID-19.

And finally, on June 5, 2020, the Randomized Evaluation of COVID-19 Therapy (RECOVERY) Trial tested hydroxychloroquine in hospitalized patients. More than 11,000 patients from 175 NHS hospitals in the UK enrolled in the trial. Out of that, 1,542 were selected for the hydroxychloroquine group and 3,132 were selected for the usual care group. Within 28 days, researchers collected data about patient improvement, hospital stay duration, and mortality.

After 28 days, 25.7% of the hydroxychloroquine group died from COVID-19. It was slightly higher than the 23.5% mortality in the usual care group. The percentages showed that hydroxychloroquine had no beneficial effects, at least, against the novel infection. The drug was also observed without a strong correlation to reduced hospital stay duration.

"Hydroxychloroquine and chloroquine have received a lot of attention and have been used very widely to treat COVID patients despite the absence of any good evidence. The RECOVERY trial has shown that hydroxychloroquine is not an effective treatment in patients hospitalized with COVID-19. Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs," said Peter Horby, chief investigator of RECOVERY Trial and professor of emerging infectious diseases and global health at the University of Oxford.



Even though the three clinical trials already extinguished hope in hydroxychloroquine for COVID-19, another team is still looking into the pre-exposure prophylaxis or PrEP for healthcare workers, instead of post-exposure prophylaxis. With HIV, people at risk of infection are advised to take PrEP. HIV PrEP is effective in protecting people from the virus, though, should only be taken by those who truly are at risk.

“You have a much better chance of preventing something with a weak drug than you have of curing a fully established infection. We would never treat anybody with it, it’s too weak. But it’s a very good prophylactic,” said Nicholas White of the Mahidol University, as quoted by Science Magazine, a peer-reviewed academic journal.

If hydroxychloroquine or another drug can be used as PrEP, then it will significantly aid medical frontliners. Worldwide, there have been casualties among healthcare workers due to COVID-19. Some of them caught the illness from patients who did not disclose critical information. Hopefully, medical researchers can find a COVID-19 PrEP soon before the global healthcare system collapses.