Hydroxychloroquine is no better than a
sugar pill at stopping health-care workers and others exposed to COVID-19 from
getting sick, the first results from a clinical trial testing the drug as a
prophylactic suggest.
In a study of 821 people who had been
exposed to someone with a confirmed case of COVID-19, 11.8 percent of people
taking hydroxychloroquine and 14.3 percent of people taking a placebo developed
symptoms. There is no
statistically meaningful difference in those numbers, researchers report
June 3 in the New England Journal of
Medicine.
“This study definitely tempers
enthusiasm for post-exposure prophylaxis among health-care workers,†says
Rachel Hess, a primary care doctor and health services researcher at the
University of Utah School of Medicine in Salt Lake City. She was not involved
in the study, but is testing hydroxychloroquine in a clinical trial of people
newly diagnosed with COVID-19.
A far larger study of the drug’s
potential to prevent disease, which involves thousands of health-care workers,
is still ongoing and expected to report results later this year.
Interest in hydroxychloroquine stems
from studies in lab dishes that have suggested that the antimalarial drug could
block coronavirus entry into cells and slow viral replication. But studies
testing the antimalarial drug against severe cases of COVID-19 largely haven’t
panned out.
A study published May 22 in the Lancet also had suggested
hydroxychloroquine carries a higher risk of death for people with serious cases
of COVID-19, leading the World Health Organization to temporarily stop one part
of a clinical trial testing the drug. But editors of the Lancet issued an expression of
concern June 3 that the study might be based on faulty data provided by a
company founded by coauthor Sapan Desai. Surgisphere Corp, based in Chicago,
refused to turn its proprietary database over to reviewers, so the other
authors of the study retracted the
paper June 4. The WHO also announced June 3 that testing
of hydroxychloroquine will resume after a safety review found no reason to
halt the trial.
Despite disappointing results from
studies of patients with severe disease, researchers were hopeful
that giving the drug earlier might have benefits (SN: 5/22/20). “There is some thought that it could still be
clinically important, but we’re less optimistic than we were before we got our
results,†says Sarah Lofgren, an infectious diseases doctor at the University
of Minnesota. Â
Lofgren and colleagues recruited
participants via the Internet. Study volunteers were mostly health-care workers
or family members who had been exposed to a person with a known case of
COVID-19 for 10 minutes or longer while not wearing a mask or eye protection.
That’s considered a high-risk exposure. Some people in the study had moderate
risk exposures, in which they were wearing masks but not eye protection when
they encountered the person with coronavirus.
Researchers asked participants to take a
total of 19 tablets over five days, assigning participants at random to get
either hydroxychloroquine or a placebo. Neither the researchers nor volunteers
knew which drugs each person received. Participants then reported symptoms and
side effects for 14 days, with follow-up surveys four to six weeks later.
Because the study began in March when
testing for COVID-19 was scarce, only 20 people in the study got tested with
PCR, which detects the virus’s genetic material, to confirm their infections.
Researchers relied on other study participants’ symptoms to determine whether
they likely had COVID-19. Studies have shown that nearly half of people who
contract the virus have mild or no symptoms. “If they were asymptomatic, we
missed them,†Lofgren says.
About 40 percent of participants who
took hydroxychloroquine had side effects, which mostly consisted of
gastrointestinal problems such as nausea, diarrhea and indigestion. Only about
17 percent of people taking placebo reported side effects. None of the side
effects reported by either group were severe. But the lack of clear benefit for
people taking hydroxychloroquine coupled with the risk of side effects led a
review board to stop the trial early for “futility.â€
Even if the difference between the two
groups crossed the threshold to be statistically important, there’s not enough clinical
evidence of benefit to suggest hydroxychloroquine can stop coronavirus
infection after exposure to the virus, Lofgren says. Lofgren and colleagues also
are finishing two other trials testing the drug at two other stages: whether it
can prevent infection when given before exposure or hold off serious disease for
those already infected.
But Myron Cohen, director of the Institute
for Global Health & Infectious Diseases at the University of North Carolina
School of Medicine in Chapel Hill, suggests that the jury is still out on
hydroxychloroquine’s preventive powers. The study results “are more provocative
than definitive, suggesting that the potential prevention benefits of
hydroxychloroquine remain to be determined,†he writes in an editorial also
published June 3 in the journal. He notes that some study participants quit
taking the drug before they had finished all 19 pills, usually because of side
effects. And there was no way to confirm that others took the drug as
instructed.
Hess says she’s waiting for other
studies to confirm or contradict this study. These findings indicate that
people shouldn’t take the drug as a COVID-19 preventative if not enrolled in a
clinical trial, she adds. Instead, wearing masks, social distancing and
thorough handwashing will best help protect individuals and communities from
infection.
