A tropical disease doctor turns his sights on the coronavirus
If all goes well, hundreds of healthcare workers across the country will soon get a package at their door containing a packet of 65-year-old pills and a set of instructions.
The pills contain either an anti-malarial medication called hydroxychloroquine or placebo, and the instructions contain the protocol for the United States’ fourth coronavirus clinical trial. The brain child of a tropical disease researcher well acquainted with malaria, the study could soon tell us if there’s a way to help protect those most exposed to the virus from falling ill.
“This is not what I do on a day-to-day basis,” University of Minnesota professor David Boulware, who normally works on HIV and tuberculosis meningitis, told Endpoints News. “But this is such a public health crisis that someone had to do something.”
Boulware began planning the trial last week as the US outbreak began. Hydroxychloroquine and its analog, chloroquine, have been used for decades to treat malaria — turning up the pH in cells and interfering with the proteins the virus uses for infections. Chinese doctors turned to it early in the coronavirus outbreak in their scramble for potential therapies, and in the last few days, as the global need for treatments has sharpened and as enough time has passed for patches of data to come out, the drug has emerged as a leading candidate to treat Covid-19.
The World Health Organization said yesterday it would be one of four drugs they test in a global, multi-arm study. Early data from a 24-person non-randomized study in France suggested it might be vastly superior to standard of care in clearing the virus (the full data complicated matters). It’s garnered proponents both in Nature and on Twitter.
Maybe worth considering chloroquine for C19 https://t.co/LEYob7Jofr
— Elon Musk (@elonmusk) March 16, 2020
Boulware’s study, though, takes a different approach than most of the handful of hydroxychloroquine clinical trials underway worldwide — and a different design, he said, than he or the FDA had ever seen.
“We had a call with FDA this morning and they were like, ‘yeah this is kind of interesting, yeah we’ve never seen this before,’” Boulware said.
Rather than treating patients who are already sick and hospitalized, the study is testing the drug as post-exposure prophylaxis, i.e. trying to prevent infection in those who have been exposed but have not yet shown symptoms. It could potentially provide a method to help protect the most vulnerable, particularly healthcare workers. An Oxford team is trying a similar idea, although not all coronavirus experts see potential.
“I think that this drug is not useful,” Stanley Perlman, who has studied coronaviruses for 38 years at the University of Iowa, wrote to Endpoints in an email.
To get the drug to places in the US where the outbreak is ongoing and exposure is highest, Boulware chose to run the study essentially online and through FedEx.
There is no trial site. Healthcare workers and others who have been exposed in the last 3 days can sign up online. They’ll receive the package at their door by 10:30 am the next day. The regimen lasts 5 days, at which point there’s an online survey. Another survey is taken at the end of 14 days. If you’re symptom-free, you’re done. If you have symptoms, the researchers send another survey asking if you’ve been hospitalized and, if so, the details of that hospital stay, and if you have a pending lab test.
Boulware publicized the treatment on Twitter and other social media. As of this morning, 70 volunteers had enrolled from more than a dozen states. If they enrollment is quick and the drug is very effective, they could have an answer in a couple weeks, Boulware said.
“We’re trying to really enroll people at very high risk of transmission, so the trial can be done quickly with the smallest number of people enrolled,” Boulware said. “If it works, great and everyone can use this. Or, if it doesn’t work, then we need to have a different strategy. That’s the concern: We don’t want to be trying random medicines and have no idea what works.”
Already, larger looks at some antivirals have muddied a once-promising picture. A New England Journal of Medicine study published yesterday testing the HIV drug combo lopinavir–ritonavir showed no benefit over standard-of-care for coronavirus patients. The French chloroquine study released full results today, revealing they had excluded 3 patients who had received chloroquine, including one who later died. Remdesivir, the Gilead antiviral that’s emerged as perhaps the leading candidate to treat coronavirus, looked initially promising when deployed against Ebola in 2014, only to later perform little better than standard-of-care when tested in a randomized trial.
Boulware isn’t banking on the drug, but he said it may be more effective in preventing infection than in treating patients who are already in the hospital.
“At that point, they’re really really sick and it may not help the patient much,” he said.
If the drug works, though, that won’t be the end of the story. When he decided to launch his study last week, Boulware was able to order enough pills for an entire course of treatment for $12. But he warned that if the drug is shown to work, demand will quickly far outstrip manufacturers’ ability to supply it.
Yesterday, Britain banned both export and hoarding of chloroquine.
“They’re going to sell a lot of it,” Boulware said of the handful of companies who make the drug. ‘There’s going to be a shortage of supply.”
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