Is it an effective defense against, or treatment for, COVID-19? Or is it a dangerous drug that could either (a) kill vast swaths of people for whom it is prescribed, or (b) kill vast swaths of people who face a shortage in their regular supply of it? The status of hydroxychloroquine, a well-known antimalarial drug, has been bandied about by politicians and advocates based on anecdotal and sometimes contradictory data for months.
Now we finally have data from an actual clinical trial of hydroxychloroquine’s effect on COVID-19. According to the University of Minnesota’s trial data, the drug has no prophylactic value in preventing development of the viral infection:
“While we are disappointed that this did not prevent COVID-19, we are pleased that we were able to provide a conclusive answer,” said Dr. David Boulware, leader of the U trial. “Our objective was to find an answer.”
Results published online Wednesday by the New England Journal of Medicine showed little difference in the onset of COVID-19 in 414 people who took hydroxychloroquine and a comparison group of 407 that took only folic acid vitamins. All participants had at least moderate risk for COVID-19 after being exposed to others in their homes or workplaces who had the illness.
There was a small difference, as 11.8% of people taking the drug developed COVID-19, compared with 14.3% of those taking vitamins, the study showed. However, that difference was considered statistically insignificant.
Even if valid, the small difference means that 42 people would have to take the drug prophylactically to prevent one COVID-19 case. That would be costly and expose people to drug side effects. The study showed that 40% experienced mild side effects such as nausea, but it allayed fears that widespread use of the drug could result in cardiac and other complications.
This study only considered prophylaxis. Another UM study is under way for treatment:
The study provides evidence only of whether the drug is effective in preventing COVID-19 onset following exposure to someone with the infection.
But what about the zinc? The backers of hydroxychloroquine have claimed that earlier anecdotal data missed the point because it didn’t include zinc supplements in its dosing. This study did review that question as well, and found it made no difference at all:
While not a primary goal, the study also found no increased protection for participants who also took zinc or vitamin C. A separate study suggested that zinc could boost the effectiveness of chloroquine, but even if that’s true, the U authors noted that most Americans consume enough zinc already so supplements shouldn’t be needed.
A single clinical trial won’t fully settle the question, especially with the relatively smallish sample in the UM study. If anything, these findings should encourage more study, as it’s now clear that the Lancet study that set off warnings about research on hydroxychloroquine was based on false data; we know now that such research can be done safely. The study on its use as a treatment can go forward, for instance, and other countries can consider larger and perhaps more diverse studies — perhaps using azithromycin, which was anecdotally supposed to support hydroxychloroquine and zinc in combination against COVID-19.
More trials might be necessary for other reasons. One of the ironies of studying COVID-19 is how tough it is to structure a normal clinical trial in a shutdown. Dr. David Boulware had to conduct the study with more remote work than usual, with medications/placebos mailed to study participants. Some of those were included based on symptoms rather than confirmation of COVID-19 infection by testing, especially early on when testing was still tough to get. “I’m sure people will come after it,” Boulware told the Star Tribune, “but the data are what the data are.”
However, this is the kind of double-blind clinical trial that generally produces much more reliable conclusions. The conclusions here are that all those who hyped it as a miracle drug and who hyped it as a lethal danger were wrong. The rest of us feel like Jen Reiner of Edina, a study subject quoted by the Star Tribune when the results of the study got published yesterday:
“A bit bummed the drug didn’t seem to work,” Reiner said, “but it had to be one way or the other.”
Indeed. For now, we can perhaps look more to a vaccine for prophylaxis, and see what Boulware’s team concludes from its study of hydroxychloroquine as a treatment. It beats jumping to conclusions … one way or the other.