With more questions than answers, hydroxychloroquine still under the microscope

By Anne Blythe

Four months ago, few would have fathomed that a 65-year-old drug would become a household name now recognized by many North Carolinians and the subject of heated political discourse.

But that’s the recent history of hydroxychloroquine.

The COVID-19 pandemic has changed everyday parlance to include such phrases as “flattening the curve,” “social distancing” and “stay-at-home orders.” It also has many debating the pros and cons of the tongue-twisting named drug touted by President Donald Trump as a potential panacea for treatment and prevention of the still mysterious virus.

The Duke University Clinical Research Institute launched a nationwide study in early April to find out whether hydroxychloroquine, known as HCQ, can be used to prevent COVID-19 infection.

The plan was to give the drug that has been used for years to treat lupus, malaria and rheumatoid arthritis to frontline pandemic workers more likely to be in the path of the novel coronavirus.

Since then, the Healthcare Worker Exposure Response and Outcomes trial, or HEROES project, has enrolled more than 13,498 participants in its registry. Some 700 people are taking either the drug or a placebo so researchers can measure its potential as a preventive medicine in the fight against COVID-19.

Who expected this dynamic?

Adrian Hernandez, vice dean for clinical research at Duke University’s medical school, spoke recently about what it’s like to run a clinical trial amid the focus and hullabaloo surrounding HCQ created by the president and others.

“Talk about a dynamic atmosphere,” Hernandez said. “No one ever expected the president to be talking about this.”

In the early weeks of the pandemic, small studies conducted in China and France touted the drug’s potential as a treatment for the novel coronavirus. Then those studies drew scrutiny and criticism for shortchanging longstanding scientific methods and protocols as researchers around the world raced to develop vaccines and treatments.

It started in mid-March when corporate bad boy Elon Musk tweeted about the drug. Then, in early April, Trump took up the banner, tweeting that HCQ, especially when taken with azithromycin, had a “real chance to be one of the biggest game changers in the history of medicine.”

Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, cautioned against putting such tremendous stock in the president’s prescription for a quick cure, noting the need for evidence-based studies over time.

On April 5, during a White House press briefing on the coronavirus pandemic response, President Donald Trump promoted the use of hydroxychloroquine. “I may take it, okay? I may take it,” he said at the time. “And I’ll have to ask my doctors about that, but I may take it.” Video courtesy: C-SPAN/ Eric Mack

Results, pauses, questions

In late May, not long after the vice president’s press secretary and the president’s military valet tested positive for COVID-19, Trump said he was taking HCQ as a preventive drug. Hernandez said the president is not a participant in the HEROES project.

Not long after the president said he had been taking HCQ for days, the World Health Organization temporarily halted its global trial of the drug, raising safety concerns.

A study of 96,000 patients hospitalized with COVID-19 done across six continents was published in the Lancet on May 22. The report in the medical journal concluded that patients given HCQ or chloroquine, a related drug, between Dec. 20 and April 14 had a significantly higher risk of death than those not given the drug.

The study also found that patients given HCQ were at greater risk for heart arrhythmias, an often-cited downside of the drug.

Call for data audit

Now there are questions about the data collected for that study by Surgisphere, a data analytics company that until recently did not have widespread name recognition. The company collected data for the study from hospital records it had procured and has added a supplement in response to questions raised by the Lancet article.

The Lancet published a note, raising concern about the data reported and stated the authors, which are not affiliated with Surgisphere, had commissioned an independent audit.

As has been the case throughout the pandemic, it can be difficult to keep up with the quick pace in which COVID-19 brings change. Not much remains the same for long — except the presence of the virus. Studies are published and then subject to quick scrutiny by academic and scientific researchers, as well as amateur sleuths.

Some of the results cause scientists to change course, others bring more questions.

Hernandez knew last week that questions were rumbling about the study in the British journal, the Lancet.

“Now we’re in this conundrum,” he said.

So many questions about the drug are the reason that Hernandez and others pushed for clinical trials in the first place. They are designed to get evidence-based answers.

The New England Journal of Medicine published results on Wednesday from a similar clinical trial done by researchers at the University of Minnesota. The study focused on 800 adults in the United States and Canada exposed to COVID-19 either because they lived with someone with the virus or worked on the front lines in health care or other jobs where they were exposed to the virus.

They were given HCQ or a placebo for five days and monitored for two weeks.

Fourteen percent given the placebo tested positive or showed symptoms for COVID-19, and 12 percent given HCQ did, leading the researchers to conclude that the drug does not prevent people from contracting the novel coronavirus.

More than a thousand health care workers from North Carolina have joined the HEROES registry, agreeing to be part of the study, according to an update provided by Duke last week.

Coach K recruits for study

The program has drawn support from university health systems across North Carolina, including the University of North Carolina at Chapel Hill and Wake Forest Baptist Health.

The researchers hope to add a broad array of workers, including custodians, nursing home staff, EMTs and kitchen staff at hospitals or clinics.

The protocol for the study excludes any participants at high risk for certain heart conditions, severe heart disease, retinopathy, severe skin reactions or people taking medications that can interact with HCQ.

Nonetheless, recent headlines about the drug could make it difficult to recruit participants. The trial organizers have posted YouTube messages from an array of health care and frontline workers to help bring on board participants.

Mike Kryzyzewski, a Duke University basketball coach with decades of recruiting experience, joined the effort, too, with a message posted on the site.

The coach then encourages them to join the HEROES registry “to help develop a preventive solution for health care workers exposed to the coronavirus.”

“Without a known treatment to prevent COVID-19, trials like this are important,” Hernandez said last week.

In addition to studying the preventive potential of HCQ, the HEROES project also hopes to take the mental temperature, so to speak, of health care and frontline workers in the registry throughout the pandemic.

“Inclusive representation in HERO research across our state’s healthcare systems means we’re asking all people who serve in all types of healthcare settings to join,” Bridget Thomas, project manager for the HERO-HCQ Trial at Wake Forest, said in a statement released by Duke on Wednesday.

“We’re seeking healthcare workers from all environments—including hospitals, outpatient and urgent care clinics, nursing homes, and in-home nursing care—to join the HERO community. This way, we can better understand how the COVID-19 pandemic impacts their physical and mental health, determine research priorities, and offer evidence-based solutions.”