Drug could be COVID-19 game-changer, but for now it’s ‘science by press release’
It’s cheap, widely available in Canadian hospitals, and, according to researchers at the University of Oxford, the only drug so far proven to help save the lives of patients severely ill with COVID-19.
The steroid dexamethasone could be a game-changer for treatment of the novel coronavirus, but without the full data from the study, Canadian physicians say they’re left to make life-or-death decisions in the dark.
The results of the clinical trial were sent around the world Tuesday in a press release, and the finding that the drug cut the risk of death by one-third for COVID-19 patients on a ventilator was heralded as a breakthrough for physicians desperate for a treatment.
“If this is truly an effective treatment, this is phenomenal,” said Dr. Isaac Bogoch, an infectious disease specialist at the University Health Network. “This would be a tremendous addition to the toolkit, which is essentially empty right now for the treatment of COVID-19.”
But for now it’s “unfortunately science by press release,” without being able to see the full study, he added.
Dr. David Juurlink, a drug safety researcher at the University of Toronto, said doctors now have to make difficult clinical decisions about using dexamethasone without being able to critically evaluate the paper in its entirety. Still, he added, the “bottom line results are extremely impressive.”
“If I had a COVID patient just needing oxygen now, I sure as hell would use this drug.” DR. DAVID JUURLINK UNIVERSITY OF TORONTO “Line up 10 doctors, you’re going to get a couple of different answers.” DR. ISAAC BOGOCH UNIVERSITY HEALTH NETWORK
“If I had a COVID patient just needing oxygen now, I sure as hell would use this drug.” The RECOVERY (Randomised Evaluation of COVid-19 therapy) trial is investigating six pre-existing treatments for coronavirus patients. In this study, more than 2,000 patients were given a low dose of dexamethasone for 10 days. The researchers also found the drug reduced the risk of death by one-fifth in patients who received only oxygen.
The study did not find that the drug had any impact for patients with mild cases of the disease. Still, researchers estimated it could have saved up to 5,000 lives in Britain if dexamethasone had been used since the start of the pandemic.
In the first 24 hours after the trial results were released, Canadian physicians and researchers debated the findings by email and on Twitter. Some are embracing the results, saying they would use it immediately at the bedside, while others urged caution.
Either way, doctors treating COVID-19 patients must now make decisions without the full weight of the evidence, said Bogoch.
“Line up 10 doctors, you’re going to get a couple of different answers,” he said.
Since the start of the pandemic, 4,034 people in Ontario with COVID-19 have ended up in the hospital. On Wednesday, there were 383 patients hospitalized with the virus, including 92 in intensive care.
Dr. Eddy Fan, a critical care physician at Toronto General Hospital, a part of UHN, said he is encouraged by the results, especially as this is a large, welldesigned global trial led by experienced scientists.
But while there is optimism among Ontario physicians over dexamethasone, Fan said he thinks many will likely have “a healthy degree of skepticism” until the final report is published.
“We want to be certain we have all the data available before we make a decision about changing the way we treat our sickest patients,” said Fan, director of critical care research at UHN and Mount Sinai Hospital.
That dexamethasone is widely used in medicine should signal to physicians that the benefits of the drug outweigh any potential harms, said Juurlink, also an internist at Sunnybrook Health Sciences Centre.
“The reason I’m prepared to use it without seeing the paper is because it’s pretty hard to hurt somebody with 10 days of dexamethasone,” he said.
“It does have side effects; it can cause blood sugar to go up, it could cause insomnia or cause people to be agitated and rarely, even psychotic. But we know of these side effects, and they are fairly uncommon, predictable and reversible.”
Currently, doctors treating COVID patients largely rely on supportive care, such as supplemental oxygen, to help them through their illness. In the absence of other treatments for such patients, Juurlink said he would rather use this drug now, and change course later, should the full trial results paint a different picture.
Unlike remdesivir, an antiviral drug developed for Ebola that an April study said reduced recovery time in hospital, dexamethason e is “cheap as borscht” and already being used in hospitals across the country for other illnesses, said UHN’s Bogoch.
He understands that it takes some time for a study to be published in a peer-reviewed journal. But, he added, the researchers could have published what’s called a “preprint,” a full study that hasn’t been submitted for publication yet or is under review. Or they could have simply published all the data online.
This is “unacceptable” at any time, but “it’s much more unacceptable right now during the course of a pandemic, where we’re truly making decisions in real time.”
A media contact for the researchers behind the Oxford study did not respond to a request for comment from the Star by deadline.
Physicians worldwide have been caught off-guard before, trying to balance the careful evidence-based scientific traditions with the need for speed in a global pandemic.
On Monday, the U.S. Food and Drug Administration withdrew emergency-use authorization for hydroxychloroquine and chloroquine — two malaria drugs that had been hailed as potential treatments — saying they are unlikely to be effective and have potential risks
The New England Journal of Medicine and the Lancet also retracted two major studies earlier this month, because of flawed data. The results of a study showing that remdesivir reduced hospital stays were also shared in a press release without the full data to support it.
Dr. Theresa Tam, Canada’s chief public health officer, said on a phone press conference Wednesday that federal health authorities are “looking forward” to seeing the dexamethasone data once it’s published and they will review it “as fast as possible” along with expert clinical care networks.
“This medication is actually something that is used in the medical care system already for people who have an inflammatory illness, and some people in the ICU are being treated with dexamethasone for certain conditions,” she said. Until then, it is available and “clinicians always have the ability to exercise clinical judgment.”
At the World Health Organization’s daily press conference in Geneva, Dr. Mike Ryan, executive director of the WHO Health Emergencies Programme, cautioned “it is exceptionally important that the drug is used under medical supervision,” and shouldn’t be taken to prevent the disease or for mild cases.
Currently, Fan and his colleagues at Toronto General are using other kinds of steroids to treat COVID-19 patients in intensive care, a decision based on previous research that has shown corticosteroids can improve the outcomes of patients with acute respiratory distress syndrome, or ARDS.
Fan said they may switch to dexamethasone, should the full data back up the RECOVERY findings, and use the same dose and regimen studied in the trial.
Dr. Bram Rochwerg, a critical care physician and the ICU’s research lead at the Juravinski Hospital, a part of Hamilton Health Sciences, said he is not surprised by the RECOVERY findings given the previous research that corticosteroids can help patients with ARDS.
“With COVID-19, the reason why some people are critically ill for weeks and weeks is because of this inflammatory cascade process in the lungs,” said Rochwerg, an associate professor at McMaster University. “Over time, the inflammation turns into lung scarring and fibrosis. Before Tuesday, I’d guess there’s about a 50 per cent split among clinicians using corticosteroids in the sickest ARDS patients. Now, I bet the majority will give them.”
Currently, doctors treating patients largely rely on supportive care, such as oxygen, to help them