KANSAS CITY, Mo. — For 30 days, Kansas City physician Michael Waxman took a daily dose of hydroxychloroquine.
Or maybe, he didn’t.
Maybe, those pills were nothing more than a placebo.
He won’t know until the end of a national clinical trial investigating whether hydroxychloroquine — the drug that keeps popping up in headlines — can prevent health care workers like him from getting COVID-19.
The study, led by Duke Clinical Research Institute, is taking place at 40 sites across the country, including the University of Kansas Medical Center.
Waxman, a pulmonary critical care physician who has worked at Research Medical Center since 1985, was the first person to volunteer through KU. That earned him the honor of being the study’s “truest guinea pig.” He did it gladly, without reservation.
“You get to see (on the) front line how bad and awful the disease can be,” Waxman said. “And if there’s something else you can do besides just help try to treat it … can you actually go that other step forward?”
But controversy and public confusion about the drug have made it difficult to recruit more volunteers needed to study the drug’s possible prophylactic powers over this new coronavirus, according to researchers at KU, Duke and other sites involved in the HERO HCQ Trial, launched in April.
Recruitment among health care workers slowed after media coverage of early studies that found hydroxychloroquine didn’t benefit COVID-19 patients. Apparently, politicians giving their two cents’ worth hasn’t helped either.
More drama came last week when a group of people wearing white lab coats stood in front of the Supreme Court in Washington, D.C., to tout hydroxychloroquine as a COVID-19 “cure.” A video of the group was banned by Twitter, Facebook and YouTube because it violated their misinformation policies.
At this point, hydroxychloroquine has become a four-letter word for some people.
“There’s been a couple of times where I talk to people and they say ‘Yeah, I’m interested, I want to participate.’ And then they say ‘Wait, wait, wait. Is this a hydroxychloroquine trial?’” said KU clinical research coordinator Maggie Messplay.
KU announced in April that it needed 500 health care workers from the Kansas City area to participate.
As of this week, researchers there have signed up 94, said Messplay, though that’s more than at many other sites across the country.
Nationwide, the trial has enrolled 1,165 participants, said a Duke spokeswoman. The goal is to reach 2,000 volunteers by the end of August.
The goal given in April was to get 15,000 health care workers involved.
The HERO study takes its name from the Healthcare Worker Exposure Response & Outcomes (HERO) registry, launched earlier this year as a way for health care workers across the United States to share with scientists their work and home life experiences as they confronted the pandemic.
The registry is still open to “all healthcare workers, including nurses, therapists, physicians, emergency responders, food service workers, environmental service workers, interpreters, transporters — anyone who works in a setting where people receive health care,” its website says.
People can sign up for the registry at heroesresearch.org.
The hydroxychloroquine trial was the first that registry members were invited to participate in; they might be invited to participate in COVID-19 vaccine trials as well.
Right now, “studies are under more pressure than ever before to quickly recruit,” Duke researchers wrote in a recent update of the hydroxychloroquine study.
“Conversations playing out in the media can create confusion, which is bad for public health, and could create unintended consequences, such as impacting recruitment for critical clinical research trials designed to help find answers about what works, what doesn’t.”
Said Messplay: “If we do this research and we realize it doesn’t work, now we know we need to pursue other prophylaxis, either drugs or just the physical barriers we can put in place between each other.”
Back in April, “we went in guns blazing, we were really excited to enroll as many people as possible,” Messplay said. “Then that infamous Lancet article was published.”
In May the online medical journal The Lancet published a study saying hydroxychloroquine was not effective in treating COVID-19, that it caused heart problems and worse, increased the risk of death in patients.
The news landed like a bomb. The World Health Organization and others halted hydroxychloroquine studies.
But there were suspicions about the findings, and The Lancet retracted the study in early June because data could not be verified by third-party peer review.
By then, though, damage had been done.
“It just took a lot of wind out of our sails,” Messplay said. “That’s how the recruitment was affected.”
Researchers involved in the HERO study got vocal about pointing out that their project is focused on preventing COVID-19, not treating it, and that unlike in other studies, these trial participants are not sick, hospitalized patients.
“It had a definite negative impact,” said pulmonologist Mario Castro, the study’s principal investigator at the KU site and vice chair for clinical and translational research at the University of Kansas School of Medicine.
“Really, it was the treatment trials that were published that showed it had no impact. Then a lot of the public interpreted that, ‘Well, why participate in a hydroxychloroquine study if it’s not helping me?’
“What we’ve had to do is kind of readjust and educate (people) that, ‘Hey, this is not a treatment trial. This is truly for people that have not acquired the infection and it’s for people that are exposed to it and this still may be a very effective prophylaxis.”
Hydroxychloroquine, sold under the brand name Plaquenil, became a subject of controversy in March when President Donald Trump touted the drug, used to treat lupus since the 1950s, as a “game changer” treatment for this new coronavirus infecting the country.
That enthusiastic endorsement — based largely on the findings of a French study later withdrawn by its authors — led to a run on the drug. Millions of lupus and rheumatoid arthritis patients who rely on it were left high and dry when pharmacies ran out.
Many hospitals that treated patients with it in the first months of the pandemic have stopped using it.
In June, the U.S. Food and Drug Administration revoked its emergency use authorization for using hydroxychloroquine, and the related drug chloroquine, to treat hospitalized COVID-19 patients, “based on recent results from a large, randomized clinical trial in hospitalized patients that found these medicines showed no benefit for decreasing the likelihood of death or speeding recovery.”
Dr. Todd Rice, a pulmonologist and associate professor of medicine at Vanderbilt University in Nashville, Tennessee, another site participating in the HERO trial, said it’s been “fascinating” to watch the drug’s ups and downs.
Back in March, when doctors were desperate to find anything that could help COVID-19 patients, “you were a devil if you didn’t give every patient hydroxychloroquine,” Rice said.
Then, the quick studies came.
Then, “there was a move of ‘this is bad,’” Rice said.
“Now, you’re the devil if you’re giving it to people,” Rice said. “And I think that pendulum which has swung back and forth a number of times has now sort of settled in the middle range — it probably doesn’t hurt people but it probably doesn’t help them, either, therefore why should we give it if it’s not helping people?”
Health care workers knew they would be in the COVID-19 crosshairs. Data from the HERO registry has proved that.
Forty-three percent of more than 12,000 health care workers who had registered as of May had been exposed to COVID-19 — 90% of those exposures came in the workplace, according to Duke.
Of those 90% exposed, 1 in 10 became infected, with Black and Latino health care workers twice as likely to contact the virus, Duke’s data shows.
“And sadly, we saw so many people around the world who were some of the first victims, the health care providers, the physicians, the nurses, the respiratory therapists, and others,” Waxman said.
“And as much as there was early knowledge of you have to protect yourself — because infection control is not a new subject — we still knew we were out there, and sure enough, in the United States, a number of health care workers also contracted the disease, and some died.
“So knowing that, is there any possibility you could prevent us from getting it?”
One of the problems with the hydroxychloroquine story, Waxman said, is that “people have been reporting next to everything they’ve been seeing, they’ve been experiencing, and there’s been an utter lack of really great research that’s been reported.
“In fact, probably a large amount of what you’re looking at is just simply observational data, assuming that it’s not bogus, as unfortunately there’s been a bit of. But even the other things are very observational and … you really need good science to try to differentiate.”
“Large, randomized controlled trials” are the only way to find out whether hydroxychloroquine can prevent COVID-19 in people who are at risk of exposure to the infection, Duke’s researchers say.
Castro said that’s key about this study.
“That’s one of the things that HERO has been combating, is that there’s very little prophylaxis information” about hydroxychloroquine, Castro said. “We are hoping now … that we’ll be able to answer this definitely with an adequate sample size.”
As with any clinical trial, safety is an issue. The FDA has oversight of the study, and a board reviews study data regularly to identify problems and make sure the FDA is notified when they occur.
Hydroxychloroquine is generally considered a safe and well-tolerated medication, Duke says.
Abnormal heart rhythms, like those mentioned in previous studies, are not common in people who are not hospitalized, Duke’s researchers say. Some studies, though, have found that some COVID-19 patients had heart rhythm disorders when they took it.
Because of that, health care workers at high risk for certain heart conditions, or who are taking medications known to interact with hydroxychloroquine, can’t participate in the HERO study, Duke says.
“Again, that’s part of the confusion in the public,” Castro said. “They hear about these very sick patients who are treated by hydroxychloroquine and having heart problems. But again, those are patients that would never get into HERO because we’re not using it for treatment purposes, and they would have been likely excluded anyway because of the medication.”
Messplay said none of the 94 people involved in KU’s trial have experienced severe side effects, and the same is true for participants across the country.
In recent months Duke opened up participation to dentists and dental office workers, home health workers and long-term care facility employees, Castro said.
Messplay still holds onto hope that KU can meet its original goal of getting 500 local health care workers signed up. But Duke’s deadline of the end of August looms.
“That would be really, really difficult,” she said. “But the thing is, we prepared for a huge storm (of participants), and then we didn’t see it.
“Everyone was working so hard. We were all working 60, 70 hours a week to get this study up and going. And then, nothing. And then crickets. Like two or three weeks after we started.
“So all of the bones are there, all the bones for this huge, successful trial are there. We just never got the momentum we expected.”
©2020 The Kansas City Star (Kansas City, Mo.)