Doctors have been searching for an effective treatment against the coronavirus since the outbreak began — doing so at a pace the pharmacology world has never seen. Debate over the safety and efficacy of emerging treatments has proceeded at an equally rapid pace, with doctors this week questioning an earlier study on the drug hydroxychloroquine (HCQ) that suggested it may have led to an increased mortality rate in the patients given it.
HCQ, while inarguably the most discussed, is just one in a sea of drugs being explored to combat the virus. As of this week, there are 2,138 clinical trials for COVID-19 treatment underway worldwide — according to a database created by experts at NYU Langone Health — including 442 in the U.S. alone.
“This is really unprecedented, both in the volume and the speed with which these different trials have been launched,” Dr. James Cutrell, an associate professor of medicine at the University of Texas Southwestern’s Division of Infectious Diseases, tells Yahoo Life. “I think it really speaks to the number of cases and just the newness of this disease.”
Cutrell has been tracking research on the pharmacologic treatments since the weeks after the outbreak began. He and others at UT Southwestern created a guide for doctors in mid-April, published in the Journal of American Medicine, outlining the clinical trials underway. Six weeks later, already a lot has changed. But the three top contenders for treatments at the moment seem clear: hydroxychloroquine, remdesivir and convalescent plasma.
To help distill down the influx of information on all three, here is what you need to know.
There is “no evidence” that hydroxychloroquine is effective
There are currently 252 clinical trials underway for hydroxychloroquine and chloroquine (the original drug from which it derives), more than any other drug. But Cutrell says there’s not yet clarity on whether it works. “We don’t have any large randomized studies to show that it is effective, but we also don’t have definitive evidence that it’s not effective — particularly as a prevention or taken early on in the disease,” he says. “There’s less thought that it’s going to be effective in people who have more severe disease, but there are still several large, ongoing clinical trials looking at it, so we may still find it provides a benefit.”
Hydroxychloroquine, one of the earliest treatments mentioned in the fight against COVID-19, has arguably been the most contentious. The antimalarial drug, which is also used as a treatment for autoimmune disorders like lupus, earned praise following multiple studies in March, including one published by the Lancet and another from the U.K., in which scientists combined HCQ with an antibiotic called azithromycin.
The drug quickly gained international attention, despite the fact that neither study claimed to have conclusive evidence that the antiviral worked. But the excitement was tempered by a small study in April showing that the drug may have increased the death rate among U.S. veterans with COVID-19. Last week, an even larger observational study seemed to bolster those concerns, noting an increase in potentially fatal heart arrhythmias with the drug. But in yet another about-face, more than 100 scientists penned an open letter to the Lancet Friday calling into question the study’s accuracy.
Cutrell says the back-and-forth proves the need for individuals and institutions to wait before “jumping too fast to conclusions” on treatments. “I think the take-home message is that the criteria we should be using to determine whether something is safe and effective are adequately sized randomized trials,” says Cutrell. “We should withhold judgment until … there is clear evidence about what the benefits and risks are of the treatment. We certainly have learned that with a lot of treatments, but probably [hydroxychloroquine] much more so than any.”
Doctors are optimistic about convalescent plasma
One of the main experimental treatments being explored for the coronavirus is what’s known as convalescent plasma. A more-than-century-old antibody therapy, convalescent plasma is a process in which the plasma cells of those who have recovered from an infection are delivered to those still battling it. There are currently 102 clinical trials studying convalescent plasma as a treatment for the coronavirus. The method has been used to treat other conditions, including emerging infectious diseases, and showed moderate success during the 1918 flu pandemic.
Cutrell says it’s too soon to tell if the treatment will work but that there are positive signs that are making doctors optimistic. “There have been publications out there demonstrating that it seems to be pretty safe to use in patients,” he says. “There was a large study that was published, over 5,000 patients, led by the Mayo Clinic … that demonstrated that the rate of severe adverse [health] events in people who received that was around 1 percent or less.”
The question now remains as to whether the treatment actually has an impact on the disease. “Most of the data that we have on the effectiveness of convalescent plasma is really restricted to just small case series or observational data in patients. So really what we need are randomized studies,” says Cutrell. “But I definitely think people are still interested in that as a treatment just given a long history of use for other conditions as well as what appears to be a good safety profile.”
Remdesivir is the “first proven effective therapy”
An antiviral delivered through an IV, remdesivir is an experimental drug created by Gilead Sciences, Inc. as a treatment for hepatitis C (HCV) and respiratory syncytial virus (RSV). The drug showed some success in combating Ebola and — as of now — remains the only drug that has shown effectiveness in a randomized, controlled double-blind study, which is the gold standard in epidemiology.
“I would say that’s the one drug now that is established and has proven efficacy or benefits,” says Cutrell. “It’s not a miracle cure; it doesn’t work for everyone. And so we still need to identify additional treatments that either can be combined with remdesivir to make the improvement faster or to reduce the mortality even further.”
Cutrell points out that the drug — which has prompted reduced duration of COVID-19 symptoms — can only be given in hospitals, which limits how many people have access to the treatment. But he says the findings are still significant and likely signal that more positive studies are to come. “Remdesivir was important because it was the first proven effective therapy,” says Cutrell. “So now, most likely, what I think we will see over the next several months is other treatments that provide incremental benefit either when added in combination to remdesivir or given to other special populations either as a preventative measure or people who have milder symptoms because these are not in the hospital.”
He adds, however, that Americans shouldn’t be banking on a treatment to stop the virus entirely. “I don’t know that we’re ultimately going to have final control of the pandemic until we identify an effective vaccine,” says Cutrell. “But I do think that we will probably continue to identify a handful of other treatments that might provide incremental benefit treatment.”
Credit: Yahoo News