The race is on to find a cure for the COVID-19 outbreak that has put our country on hold. Medical experts and researchers have united on a global front to conduct hundreds of clinical trials that could help remedy the coronavirus pandemic.
With a vaccine months and months (perhaps even more than a year) away, health care providers have turned to prescription medications as a way to mitigate COVID-19 symptoms. Two concerns exist with this exploration: potential risks and adverse effects and a shortage for patients who rely on those drugs for other illnesses and diseases.
The National Institutes of Health published COVID-19 guidelines with recommendations for therapeutic options under investigation for potential treatment options. We took a deep dive into the effectiveness and safety of these medications as a way to better inform you.
Be Wary of Misinformation
Before we start, the U.S. Food and Drug Administration warns you shouldn’t buy or take any product to prevent or treat COVID-19 unless it’s both from a legitimate source and authorized and prescribed by your health care provider.
It’s important to be aware of the intended use, effectiveness, and safety of any prescription drug or supplement. There’s plenty of information — and misinformation — out there about which drugs can treat COVID-19.
Because this pandemic is affecting millions of Americans, there’s a heightened sense of interest each time a news broadcast, newspaper article, or research institute publishes a study on possible COVID-19 remedies. As a result, these potential solutions can spread like wildfire.
In what has become a near-daily occurrence, the FDA, in conjunction with the Federal Trade Commission, is issuing warning letters to businesses that sell products with false or misleading claims related to the coronavirus. For example, companies selling herbal supplements, essential oils, and CBD products market them as a way to help prevent and treat COVID-19.
The FDA also warned against the dangerous side effects of products containing chlorine dioxide. More recently, a federal judge ordered a temporary injunction against a Florida church selling bleaching agents that claimed to remedy COVID-19.
Businesses are marketing these "Miracle Mineral Solutions” products, which claim to treat serious diseases such as cancer and HIV/AIDS, as a possible defense against COVID-19. Sold as kits, the products contain 28% sodium chlorite in distilled water and require an acid (something as simple as lemon juice) as an activator. The result is chlorine dioxide, which can cause respiratory failure, life-threatening low blood pressure, and acute liver failure, among other symptoms.
Researching Drug and Treatment Options
As a general rule of thumb, the FDA won’t approve a drug or treatment option unless it has data and research to prove safety and effectiveness. The research must be extensive (think thousands of participants and multiple phases of a trial), which makes it difficult to put stock into studies you may see in the news that have only a few dozen patients.
Since the coronavirus hit China in December 2019, the FDA has received nearly 1,000 inquiries and proposals for therapeutic agents. The clinical trial list grows by the day. There are at least 72 active trials and an additional 211 in the planning stage, with more than a dozen federally-funded clinical studies related to COVID-19.
Some trials are further along than others. The FDA is reviewing 19 therapeutic COVID-19 treatment options. This list includes emdesivir, hydroxychloroquine and chloroquine, sarilumab, convalescent plasma, and hyperimmune globulin.
The Truth About Hydroxychloroquine and Chloroquine
Unless you have, or know someone who has, malaria, lupus, or rheumatoid arthritis, you’ve likely never heard of hydroxychloroquine sulfate (Plaquenil) or chloroquine phosphate (Aralen Phosphate). That is until President Donald Trump labeled it as a potential game changer in treating COVID-19, thus creating unprecedented demand (30 million doses across U.S. cities and states).
But, beyond the headlines, what do we know? Hydroxychloroquine and chloroquine are oral medications used to prevent and treat malaria. Hydroxychloroquine, which also helps treat lupus and rheumatoid arthritis, is a less toxic, and therefore safer, version of chloroquine.
In the biggest pushback to date, the NIH recommends against using hydroxychloroquine combined with azithromycin because of the potential for toxicities. Azithromycin, better known as a Z-Pak for short, is an antibiotic used to treat a variety of infections. The FDA recently issued a warning for the off-label use of hydroxychloroquine or chloroquine. More specifically, research shows taking hydroxychloroquine or chloroquine by itself, or in combination with azithromycin, can cause irregular heart rhythm problems such as QT interval prolongation, ventricular tachycardia, and ventricular fibrillation.
For now, the FDA acknowledges you can only limit the risks when administering these drugs in a clinical trial or hospital setting. Patients hospitalized with severe COVID-19 symptoms who don’t have access to a clinical trial can still take the drugs. The FDA issued an Emergency Use Authorization for hydroxychloroquine or chloroquine donated to the Strategic National Stockpile.
Initial lab studies found hydroxychloroquine or chloroquine could help prevent COVID-19 from multiplying and causing harm in our bodies. However, mixed results followed. Trials in Brazil, France, and Sweden were halted due to complications. A quarter of the 81 patients in Brazil experienced heart rhythm issues when taking a higher dose.
Starting in May, the NIH will conduct one of the largest studies to date in a randomized, double-blind, placebo-controlled trial with 2,000 participants. These trials are telling because neither the patient nor the physician knows if you’re getting a combination of hydroxychloroquine and azithromycin or a placebo. A randomized, blinded, placebo-controlled Phase III study from the National Heart, Lung, and Blood Institute will provide data from 510 patients later this summer.
In the biggest positive news to date, early clinical results for the IV antiviral drug remdesivir showed it can help treat COVID-19. Further research is needed, but the news that came out in late April has medical experts cautiously optimistic.
A Phase III randomized, double-blind, placebo-controlled study conducted by the National Institute of Allergy and Infectious Diseases (NIAID) showed patients taking remdesivir recovered from COVID-19 by 31% (symptoms ended and patients were discharged after 11 days, compared to 15 days for patients who received a placebo). Remdesivir also decreased the mortality rate by 3.6% (11.6% in patients who took the placebo versus 8% of patients who took remdesivir).
While the results are modest, Dr. Anthony Fauci, director of the NIAID, acknowledged during a late-April press briefing how the findings were good news.
“What it has proven is a drug can block this virus,” Dr. Fauci said of the study, which included 1,063 patients.
Before the trial even started, preliminary research indicated remdesivir could block the replication of COVID-19 by halting RNA transcription. That outlook looked murky in mid-April after a trial in China led by drug manufacturer Gilead found unsuccessful results due to side effects and no noticeable benefits. Gilead is awaiting the results of another study, a Phase III open-label trial of 6,000 COVID-19 patients with severe symptoms.
Additionally, a clinical trial is studying the antiviral IV effects galidesivir has on COVID-19 patients. Galidesivir is an adenosine nucleoside analog that blocks pathogens found in diseases such as Ebola, yellow fever, and Zika virus. In Japan, Fujifilm is testing favipiravir as a COVID-treatment. Approved in 2014 to treat influenza, the drug never hit the market due to concerns of causing birth defects.
Convalescent Plasma and Hyperimmune Globulin
Your body produces antibodies as a defense mechanism to fight off viruses. Antibody tests, or serological tests, can determine if you’re dealing with an active or prior infection. Not only does this test give medical experts a better idea of who may have been a carrier, it also can help lead to treatment options.
While convalescent plasma isn’t a prescription drug, limited data from China shows this antibody-rich product may lessen the severity or remedy COVID-19 faster. You can then take the antibodies from a patient who has already recovered from COVID-19 and transfuse them to someone needing active treatment. A single 200 mL dose of plasma helped improve the symptoms in some patients.
Considering the positive outlook, the FDA is now encouraging patients who recover from COVID-19 to donate plasma to help develop blood-related therapies. One donation can help up to four patients. Visit this Red Cross website to learn more about eligibility and where to donate. You’re eligible to donate plasma two weeks after you’ve recovered.
The National Institute of Allergy and Infectious Diseases is also studying hyperimmune globulin, which is a biological product — any pharmaceutical manufactured from a living system or things such as sugars, proteins, or nucleic acids — from plasma.
On a broad scope, immunomodulators help regulate the immune system by reducing inflammation. Medical experts have researched and studied categories of drugs that could help treat COVID-19, including:
- Interleukin-6 inhibitors
- Interleukin-1 inhibitors
- Janus kinase inhibitors
Interleukins, a group of cytokine proteins, attach to your cells and cause inflammation (presented as lung inflammation in COVID-19 cases). In certain instances, your body produces excessive amounts, known as cytokine release syndrome or cytokine storm, leading to severe infection and organ failure. Interleukin-6 and interleukin-1 inhibitors help prevent the production of inflammatory chemicals. Kinase inhibitors block the proteins that trigger inflammation.
However, the NIH recommends against using baricitinib for the treatment of COVID-19 because of its broad immunosuppressive effect. They didn’t take a stance for or against using anakinra, sarilumab, siltuximab, or tocilizumab due to insufficient clinical data.
Meanwhile, various clinical trials exist to test these drugs. A Phase III open-label study of 342 patients is evaluating the effectiveness of tocilizumab, tocilizumab and anakinra, siltuximab, siltuximab and anakinra, and anakinra on restoring lung homeostasis.
A Phase II study of sarilumab has 400 participants, while a Phase III open-label trial of 310 participants is comparing the efficacy and safety of methylprednisolone (a steroid used to treat inflammation) compared to tocilizumab in patients who are at risk of cytokine storm. A phase III randomized 30-day study of tocilizumab was recently sponsored by Emory University in Georgia.
The FDA recently issued a letter over concerns about the potential misuse for the antiparasitic drug ivermectin. This article on ivermectin and its possible impact on SARS-CoV-2 sparked concern from the FDA that people were misusing the drug.
In humans, ivermectin (Stromectol) can treat parasites and skin conditions. It also prevents heartworm disease and treats certain parasites in animals. The FDA’s concern stemmed from people using ivermectin for animals, thinking it’s a safe substitute for ivermectin intended for humans.
HIV protease inhibitors
Lopinavir/ritonavir (Kaletra) tablets have become a popular form of HIV treatment. This combination drug helps your immune system by limiting the amount of HIV in your body. Drug manufacturers added ritonavir to the tablet to boost the effectiveness of lopinavir.
At this time, the NIH recommends against using lopinavir/ritonavir for the treatment of COVID-19 due to unfavorable pharmacodynamics and negative clinical trial data. A March study from China concluded lopinavir/ritonavir provided no benefits.
Addressing the Unintended Consequences
There are now shortages of hydroxychloroquine and chloroquine, which means patients who use these drugs daily may have trouble filling their regular prescriptions. On April 7, the FDA approved an Abbreviated New Drug Application for hydroxychloroquine sulfate tablets as a way to address a surge in demand. Note that the FDA didn’t approve this for COVID-19 treatment, rather, it addressed demand for malaria, lupus, and rheumatoid arthritis patients who rely on hydroxychloroquine and chloroquine.
The FDA also published specific product guidelines to help increase generic drug production of these two medications. The organization will prioritize the review of Abbreviated New Drug Applications for chloroquine phosphate and hydroxychloroquine sulfate.
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