UPMC will test the drug president is taking
President Donald Trump raised eyebrows — and controversy — Monday by announcing he was taking a daily prophylactic dose of hydroxychloroquine to prevent COVID-19.
A clinical trial involving UPMC will soon be underway to test the wisdom of that idea.
Dr. Bryan McVerry, a UPMC and University of Pittsburgh pulmonary and critical care medicine physician, said UPMC will participate in the upcoming HERO clinical trial — “Healthcare Worker Exposure Response & Outcomes of Hydroxychloroquine Trial (HEROHCQ)” — which involves multiple research centers.
The trial will test whether the drug can prevent COVID-19 infections among health care workers. It represents one of four trials involving UPMC to test whether hydroxychloroquine (HCQ) or chloroquine has any benefits in treating COVID-19.
Doctors near and far continue raising concern about Mr. Trump’s public announcement promoting HCQ, given insufficient evidence of any benefits against COVID-19.
Furthering that concern are the drug’s potential side effects, including potentially fatal cardiac arrhythmia.
Dr. McVerry simply emphasized that “people should take these medications only in the context of a clinical trial,” even if the focus is its use as a prophylactic treatment.
“I know I wouldn’t take it as a physician outside of a clinical trial setting,” he said.
For now, UPMC also is, or will be, participating in three other clinical trials to test HCQ as a COVID-19 treatment, which could shed light on the controversy.
• REMAP-COVID is a previously announced trial that’s operating “on the fly” to determine which drugs or combinations thereof, including HCQ, work best against the infection.
• The ORCHID trial (“Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease”) also involves multiple sites that are testing HCQ as a treatment for patients hospitalized with the infection.
• The HAZCOVID trial will help determine whether HCQ and azithromycin, an antibiotic, could help prevent patients with COVID-19 from being hospitalized.
In addition, the University of Minnesota is working to determine whether HCQ “can help in preventing or treating COVID-19 disease” in the general public.
“There is a lack of strong, human data for this drug in the setting of COVID-19 disease, so this study is aimed at providing an important and timely answer,” the study introduction says.
Pro(phylaxis) and Con(troversy)
Doctors and medical officials continue with concern about Mr. Trump’s public pronouncement that he’s taking HCQ.
“The words of celebrities and politicians are powerful, but we need to ensure we follow the data and ensure science and evidence are guiding our treatment,” said Dr. Tom Walsh, an Allegheny Health Network infectious disease specialist.
“The concern to me is any person not in the medical field promoting an unproven drug with potential for harm and in an anecdotal way, and not as part of a clinical trial,” he said, noting the need in testing novel drug therapies “to do our best to enroll patients in available clinical trials to best determine safety and efficacy of these agents before promoting their widespread use in an anecdotal manner.”
It has long been determined that clinical trials are necessary to gauge a drug’s safety and efficacy, he said. HCQ, an off-label drug for COVID-19, historically has been used to treat malaria.
But Dr. McVerry said the jury is out on HCQ’s effectiveness against COVID-19. “All the studies to date have weaknesses and challenges,” he said, noting the lack of completed randomized, placebo-controlled clinical trials to verify or dispel its effectiveness.
On May 12, the National Institutes of Health also said there’s “insufficient clinical data to recommend for or against using chloroquine or hydroxychloroquine” as a treatment, except in the context of a clinical trial.
Dr. Walsh also said the Infectious Disease Society of America has found insufficient evidence to support HCQ or chloroquine as COVID-19 treatments, with support for their use only in clinical trials.
“But outside that, it is not recommending their use at this time with the information we have,” he said, noting that physicians at AHN initially used HCQ occasionally in treating patients. “But with recent evidence showing a lack of benefit with potential harm, many have backed off from its use.”
He said 11,000 papers have been published about COVID19 in recent months, but many were poorly done, anecdotal or not yet peer-reviewed.
One observational report, yet to be peer-reviewed, did gain international attention in showing a higher mortality rate among COVID-19 patients in U.S. Veterans Health Administration medical centers who were treated with HCQ, as compared with those who weren’t.
The study — “Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized With Covid-19” — received NIH funding and involved 368 cases through April 10.
Along with standard supportive management, three groups of patients were treated with HCQ alone, without HCQ, or with both HCQ and azithromycin, with results focused on deaths and how many patients eventually required mechanical ventilation.
The death rate was about 28% for those on HCQ, 22% of those receiving both drugs, and 11.4% for those receiving no HCQ.
In addition to documenting a higher mortality rate in patients treated with HCQ alone, the study also found no evidence that HCQ, either with or without azithromycin, reduced the risk of mechanical ventilation in hospitalized patients.
“These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs,” the study concluded.
Among more recent research, a Chinese study showed that low doses of HCQ reduced death in critically ill patients with COVID-19.
But two French studies recently found no treatment success with HCQ with 10% of all patients having their doses discontinued because of modifications of electrical activity in their hearts.
Heart of concern
Such arrhythmia represents the key concern with HCQ, given its potential to “alter the way electricity is conducted through the heart,” Dr. McVerry said.
Specifically, he said, it can affect the “QT interval” — the time between contraction in the heart’s lower ventricle and relaxation. The drug, however, can lengthen that interval and potentially lead to cardiac arrhythmia, a potentially fatal condition.
For that reason, Dr. McVerry said, clinical trials focused on HCQ often exclude participants with arrhythmia or other heart conditions.
Conclusions, for now, about HCQ’s effectiveness as a treatment are wanting. That heightens concern about public endorsements of the drug.
“Right now, we don’t have any data that there’s any clinical, meaningful benefit to hydroxychloroquine in the management of COVID-19,” Dr. Walsh said. “We need better designed studies to allow us to draw more firm conclusions. But at this time, the available evidence does not support its widespread use.”