Curbing the enthusiasm for new COVID-19 treatments

A year into the COVID-19 pandemic in Canada, doctors are learning how to help keep more patients alive, but the proven treatment options remain limited.

So what does work?

The U.K.’s ongoing Randomised Evaluation of COVID-19 Therapy, or RECOVERY trial, tests existing drugs as potential therapies to treat COVID-19. Its investigators proved that giving the widely available steroid medication dexamethasone to hospital patients severely ill with COVID-19 can save lives.

Back in June, RECOVERY released a press release that included key details for applying the information and the full study was published in the New England Journal of Medicine a month later.

Currently, steroids such as dexamethasone are the only drug treatments for COVID-19 listed as “most beneficial” in a review that’s continually updated in the BMJ.

One thing researchers found was the benefit of using steroids to treat COVID-19 depends on the severity of a person’s case. The drug’s benefits only outweighed the risks in patients who were sick enough to need oxygen treatment, not those recovering at home, the research suggests.

Dr. Lynora Saxinger, an infectious disease physician in Edmonton, follows the advances in treatments and how they’re communicated.

“There’s been a lot of pressure to say, ‘Hey, we found something possibly useful, we should share it immediately,” she said.

“Enthusiasm travels so quickly and becomes ingrained before you even have a chance to really support whether it’s a good idea. Then you’re facing a bit of a battle to actually calm down enthusiasm if the data are less strong than the press release really suggested.”

Doctors who treat people with COVID-19 in hospital wards, intensive care units and out in the community continue to juggle conflicting clinical trial results — sometimes for the same treatment based on studies in different countries — most of which feature data from a small numbers of patients.

Have a question about COVID-19? CBC News is live in the comments now.

A patient with COVID-19 rests in an isolation room at a hospital in Bogor, Indonesia, on Tuesday. Currently, corticosteroids such as dexamethasone are the only drug treatments listed as ‘most beneficial’ in a prominent published review. (Willy Kurniawan/Reuters)

To try to make sense of the small numbers, clinicians follow their training to assess what’s known about the drug and apply it to their patients’ cases. That’s why “Show me the data” is a refrain doctors use when weighing treatment options for patients with COVID-19 in the face of promising press releases that are short on key details.

At this point in the pandemic, Saxinger said, the norm of presenting science by press release needs to be questioned because there’s an alternative. That is, press releases can be accompanied by what are known as preprints, or draft manuscripts that haven’t been checked for errors and include all of the available data and a study’s methods, so clinicians can assess the merits for themselves, just as the RECOVERY trial investigators do.

Last week, for example, Canadian hospitals put out press releases about two potential treatments: a common blood thinner for patients with moderate COVID-19 and colchicine, an oral medication used to treat gout.

Both announcements were based on the results of clinical trials that have yet to be peer reviewed or published in a medical journal.

Dr. Zain Chagla, an infectious disease physician in Hamilton, Ont., and an associate professor at McMaster University, recently experienced the mismatch between patient expectations for a new treatment and what he could offer firsthand.

“When you put out a press release on Friday night and your patients that test positive for COVID on Saturday are saying, ‘OK, where’s my colchicine?’ it’s very hard … to counsel them appropriately.”

Treatment hype

In the early days of the pandemic, when clinicians were trying to figure out what to do on the fly, enthusiasm led to missteps, Saxinger said.

Hydroxychloroquine, an anti-malarial drug, is an obvious example. In the spring, U.S. President Donald Trump hailed it as a game-changer in the fight against COVID-19. But the RECOVERY trial showed hydroxychloroquine did not benefit hospitalized patients

“I think the nail’s in the coffin on that one,” she said.

Chagla and Saxinger divide potential treatments for COVID-19 into a few main categories:

  • Antivirals such as those used to treat HIV, the virus that causes AIDS.
  • Monoclonal antibodies that mimic a natural antibody and were one of the treatments Trump received.
  • Convalescent plasma, which is plasma from people who have recovered from COVID-19 that contains different types of antibodies to fight the virus.
  • Immunomodulators such as interferon that aim to quell the “cytokine storm” that can lead to life-threatening complications with COVID-19.

Saxinger puts these potential treatments in the too-soon-to-tell group because larger or better trials are still needed. 

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The RECOVERY trial recently closed recruitment for its convalescent plasma study. In Canada this week, Dr. Donald Arnold, a hematologist at McMaster University who is helping lead Canada’s Convalescent Plasma for COVID-19 Research, or CONCOR trial, said the study is ongoing.

Canadian Blood Services (CBS) and Héma Québec supply convalescent plasma to doctors caring for patients with COVID-19 as part of CONCOR. CBS has said not all plasma from those who have recovered from the illness can be used as a therapy because some people might not have enough antibodies to protect others. 

Chagla and Saxinger both said ivermectin, an anti-parasite drug, also needs further study in clinical trials.

“For a single trial to be truly practice changing, it has to be pretty watertight,” Saxinger said.

In the case of ivermectin, Saxinger said the research so far was based on a small number of people. Some participants were also given steroids, making it hard to tease out the impact of the anti-parasite portion of the treatment.

Also, earlier test tube-based research into ivermectin used much higher concentrations than what’s given to humans, Saxinger said. Giving highly concentrated drugs to people can often be too toxic and result in side-effects.

Most large clinical trials for COVID-19 treatments that have reported results so far have been for patients hospitalized with the illness.

But most people recover at home. 

Last week, Canadian and international researchers with the COLCORONA study of colchicine put out a press release about the effects of the gout drug in outpatients with COVID-19. Saxinger said she’s “provisionally excited” but awaits more data to draw any conclusions about the use of colchicine.

Chagla said outpatient COVID-19 studies are beneficial because they keep people out of overburdened hospitals. 

A stretcher sits outside the emergency entrance of St. Paul’s Hospital in Vancouver on Jan. 5. Medical treatments against viral illness will always be disappointing compared to prevention, Dr. Lynora Saxinger says. (Ben Nelms/CBC)

But such multi-centre studies running in multiple countries can also be difficult to set up, especially since health-care systems are already stretched. Contracts and insurance paperwork can also bog down the trials and could be eased by regulators such as Health Canada, he said.

“Outpatient trials are super hard to fund,” Chagla said. “It’s hard to navigate.”

Blood thinners

Dr. Kwadwo Kyeremanteng, an intensive care and palliative care physician in Ottawa, said many patients critically ill with COVID-19 were having to go on dialysis due to blood clotting. It was a surprising feature of the disease last spring.

“We aggressively began putting blood thinners on board earlier in their course,” Kyeremanteng recalled. “This is more subjective, I would say, but it appeared that patients were doing better as a result.”

Blood thinners continue to be used to treat moderate COVID-19 in hospitalized patients. 

Despite all of the advances in treatments, Saxinger sees greater potential in prevention from public health measures such as physical distancing, masking and staying close to home while Canada reaches better vaccine coverage.

“At the end of the day, medical treatments against a viral and inflammatory illness are always going to be disappointing compared to just preventing the illness,” she said. “Any kind of treatment that reduces really severe outcomes doesn’t actually reduce people getting sick and doesn’t actually reduce people spreading it to others.”

Have questions about this story? We’re answering as many as we can in the comments.

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