But for some researchers, running such trials is becoming more difficult because of the controversy around the drug.
Missed opportunity
Dr. Jon Giles didn’t expect to have any problems drumming up interest in his clinical trial testing if hydroxychloroquine can help prevent COVID-19.
“We were getting calls all the time from people who were interested,” says Giles, an epidemiologist and rheumatologist at Columbia University.
For his study, Giles planned to give a short course of the medication to people who were “household contacts” of COVID-19 patients. Like many of the ongoing trials, it would be randomized with a control group.
By the end of April, Giles was ready to start enrolling people. But his team ran into a problem when they started calling potential participants.
"Pretty much everybody said, ‘Well that’s the drug that’s dangerous to your heart,’ or, ‘I talked to my friends and they said don’t take it,’ or that ‘I saw on TV it’s dangerous,’ " says Giles.
Just a month earlier, he says demand for the drug was soaring. Some patients with autoimmune conditions couldn’t even get their prescriptions filled, after Trump spoke enthusiastically about the drug.
**In April, the FDA issued a warning about using the drug for COVID-19 patients without strict medical supervision in a hospital or as part of a clinical trial. The agency had received reports of serious heart-related adverse events and death in patients with COVID-19 receiving hydroxychloroquine and chloroquine.
But the back-and-forth headlines and the ongoing political wrangling seemed to make people wary of the medication, Giles says, even in the context of a carefully run clinical trial.
“It became almost impossible to get anyone interested,” says Giles.
Giles says the committee overseeing his study added a new requirement: that study participants needed to have had an electrocardiogram within the last year.
As a rheumatologist, Giles knows the medication better than most doctors because he prescribes it to many of his patients.
“It’s a very, very safe drug; it’s been used for over 75 years,” he says. “When I give someone hydroxychloroquine, I don’t get an ECG or do blood monitoring.”
Giles was planning to enroll otherwise healthy people and screen out anyone who could be at risk of heart problems. But that new requirement, plus the negative press, made it too difficult to find study subjects.
He gave up on doing the study. He says it’s a missed opportunity.
“It’s not unreasonable to think that a short course of this drug might have some protective ability,” he say**s.
Risks and potential
The concern over cardiac risk for hospitalized patients is real, says Dr. Mark Poznansky, director of the Vaccine and Immunotherapy Center in the Infectious Disease Division of Massachusetts General Hospital. Even though the drug has been used safely to prevent malaria, he says, “that is very different from using the drug in acutely ill patients with COVID-19.”
He recently published a review of the evidence for using hydroxychloroquine to treat COVID-19 that casts doubt on its effectiveness.
“The data up to date … doesn’t make one entirely optimistic that we are going to find something different in a clinical trial,” he says.
Poznansky notes a recent study of nearly 1,400 people with moderate to severe COVID-19 found no benefit and concluded that the drug should not be routinely used on patients.
He says the drug should only be used in the context of clinical trials “or under strict compassionate use, in order to do no harm.”
Still, Poznansky doesn’t rule out that further well-designed trials could turn up better results.
‘The virus doesn’t care about politics’
At Henry Ford Health System in Detroit, cardiologist Dr. William O’Neill says enrollment for their clinical trial studying hydroxychloroquine to prevent COVID-19 plummeted in late April.
“It really caused a huge problem for us,” O’Neill says. “It set us back probably a month.”
O’Neill attributes the drop in enrollment to the FDA warning and a highly publicized study of over 300 hospitalized veterans with COVID-19. The authors of that study found the drug did not reduce the need for a ventilator and even linked hydroxychloroquine to higher death rates. However, the study wasn’t a rigorous controlled trial and the results weren’t peer-reviewed.
“That was interpreted as a warning that the drug is dangerous,” says O’Neill. But he says, using it for prevention is a different matter than treating already sick patients. “Everything that we see about hydroxychloroquine suggests that the earlier you use the drug, the more likely it is to be effective.”
**O’Neill says the fact that President Trump is touting this drug means it now has become a political flashpoint.
“It has made people absolutely committed to proving him wrong,” he says.**
