Dr. Michael K. Paasche-Orlow, an internist and researcher at Boston Medical Center, said that because of the politics surrounding the drug, he is having trouble recruiting participants for two studies — one examining whether hydroxychloroquine can help people who have tested positive for COVID-19 but are not hospitalized, the other seeing if it can prevent illness in people who have been exposed.
The studies are among some 200 research projects around the world examining hydroxychloroquine’s efficacy against an illness that, so far, has no established treatment or cure.
Paasche-Orlow’s studies, both part of national multicenter trials, have recruited only a fraction of the needed participants. “If this stuff wasn’t in the news all the time, it would be going much better,” Paasche-Orlow said. “A ton of people say, ‘What? That’s the stuff the president is taking.’”
And yet there’s good reason to ask whether hydroxychloroquine might be helpful with COVID-19. In the laboratory, the drug prevents the coronavirus from entering cells and replicating.
Hydroxychloroquine is not new or untested; it’s been on the market for decades, used to treat and prevent malaria. It is also prescribed for two autoimmune diseases, lupus and rheumatoid arthritis. For those patients, it tamps down the immune system, raising the possibility the drug might similarly mitigate the immune overreaction that causes the most deadly COVID-19 symptoms. It’s considered safer than chloroquine, a similar antimalarial.
“It does have a very well-established safety record,” said Dr. Christine M. Johnston, director of the University of Washington’s Virology Research Clinic and leader of the national study that Boston Medical Center is part of. “It’s a safe drug,” Johnston said.
Such comments might come as a surprise, given news reports.
In late April, the US Food and Drug Administration warned against using hydroxychloroquine for COVID-19 outside of research studies. Dr. Anthony Fauci, the nation’s top infectious disease specialist, told CNN Wednesday that hydroxychloroquine is not effective, based on current data. The World Health Organization this week paused a hydroxychloroquine study after a recent large trial suggested the drug may cause harm.
The top concern with hydroxychloroquine is its effect on the heart. In some patients it causes electrical disturbances of the heartbeat that can lead to arrhythmia.
Is this risk greater than the potential benefit for COVID-19 patients? The studies done so far are of such poor quality that no conclusions can be drawn from them, according to the authors of a review published Wednesday in the Annals of Internal Medicine.
Of the 23 studies completed by May 8, only four were randomized controlled trials, the gold standard of medical research in which a drug is given to one group of patients, a similar group gets a placebo, and doctors track the differences in how each group fares. But even those four trials all had major flaws, as do the studies published since May 8, said the review’s lead author, Dr. Adrian V. Hernandez of the University of Connecticut School of Pharmacy.
The research so far fails to clearly show hydroxychloroquine’s effects on COVID-19, because other factors could have accounted for the differences among patients. For example, in studies that lack a comparison group, doctors whose patients were doing poorly may have been more willing to give them an unproven drug. So any negative results may merely reflect that sicker patients received it.
Not only were the study designs flawed, the findings were contradictory. Some found no effect, some linked the drug to bad outcomes, including death, and a few found positive effects.
“We know that it’s not poison. People have taken it for a long period of time,” said C. Michael White, another author of the review and head of UConn’s Department of Pharmacy Practice. “But we can’t say the benefits are going to be worth those risks because we can’t say there’s any benefit.”
Studies completed so far have all involved hospitalized patients, people who were very sick. None examined whether hydroxychloroquine might ease symptoms in outpatients or prevent illness in those who have been exposed.
Those are the questions being addressed in the two Boston Medical Center studies.
The hospital is one of six medical centers participating in a national randomized controlled trial funded by the Bill and Melinda Gates Foundation. The study aims to recruit 630 patients who recently tested positive for COVID-19, and see whether those who take hydroxychloroquine, or the drug combined with an antibiotic, are more likely to avoid serious illness. Since enrollment started in mid-April, researchers have signed up only 10 percent of the number of participants needed.
People don’t know what to believe, said Johnston, of the University of Washington. “And it’s also difficult when one day you’re hearing it’s a miracle cure drug, the next day you’re hearing it’s unsafe.”
To reduce the likelihood of harm, people with kidney or heart problems are not allowed to participate. And all participants are intensely monitored — despite never coming into the hospital because of pandemic social-distancing requirements.
Each participant receives, via courier, a pulse oximeter to check blood oxygen levels, a thermometer, materials to swab their nose, and an EKG machine the size of a pack of gum. The EKG machine connects via bluetooth to a smartphone, and each day patients send the researchers data about their heart’s electrical activity.
The second study at Boston Medical Center, also led by the University of Washington, is examining whether people who may have been exposed to the coronavirus can avoid getting sick if they take hydroxychloroquine.
Recruitment for this study has also been slow, with only about 400 of the 2,000 needed enrolled, said study leader Ruanne Barnabas, associate professor in global health and medicine at the University of Washington.
In both studies, patients are enrolled for only 28 days. “One of the main reasons we would like to recruit quickly is so we can have an answer for the fall,” Barnabas said, “We need to break the cycle of transmission from infected to susceptible people.”
Paasche-Orlow, the Boston Medical Center researcher, notes that several other drugs may be helpful, but hydroxychloroquine is getting excess attention. He wishes the research agenda was being coordinated nationally. Hydroxychloroquine, Paasche-Orlow said, is “a good horse to bet on. It can’t be the only horse to bet on.”
Felice J. Freyer can be reached at firstname.lastname@example.org. Follow her on Twitter @felicejfreyer