Manitoba team embeds research in COVID-19 care

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This article was published 14/12/2020 (1916 days ago), so information in it may no longer be current.

As COVID-19 hospitalization rates in the province continue to push intensive care units beyond their limits, a small team of local researchers is chasing the virus most of the world has been told to avoid at any cost.

These researchers are part of a COVID-19’s patient worst-case scenario: hospitalization.

Once you are admitted to hospital, a process begins. Staff will let Manitoba’s COVID-19 clinical trial team know a new patient has been admitted, and after the go-ahead from a physician, the patient may be approached by a research co-ordinator.

You — or your family, should you be unable to consent — will receive a run-down of the trials, what they require from the patient, how long they will last. Should you sign up, you will be taking part in an endeavour the scientist heading the trials believes will revolutionize how we administer health care.

“We’re embedding clinical trials into care, and that’s totally new,” said Dr. Ryan Zarychanski, a critical-care physician and clinician-scientist.

“We’re using novel trial designs that have never been used before that are likely to change the face of clinical research forever, and it’s come out of Manitoba.”

Even as the vaccine seems to be getting closer to distribution every day, the work hasn’t slowed down. Should widespread distribution hit the late 2021 timeline set by the province, that still leaves months where people remain vulnerable to the virus.

“All these people continue to die each day, and if they don’t, they get admitted to hospital,” he said. “If we can reduce the strain on the health-care system, get our health-care system functioning again, elective surgeries done again, health-care workers back to their regular jobs, people dying less every day, then we’ve succeeded in this.”

Therapies will also be needed for those whose immune systems won’t be able to reap the full effects of the vaccine — and for those who choose not to take it.

“Vaccines are only so effective, and only so many people will get them — because either they’re anti-vaxxers, and God help them, and when God can’t, these therapies will — and many people do not mount immune responses to vaccines because they have cancer, because they have immune deficiencies, because they’re immuno-suppressed or because they have rheumatoid arthritis or some other autoimmune disease,” Zarychanski said.

“Those therapies will still be really needed in those individuals. There’s lots of good reasons to keep going.”

Patients are enrolled in clinical trials every day — Zarychanski noted a very small percentage refuse to take part in trials, including some who cite religious reasons and some who are receiving palliative care — and from there usually receive at least one of the experimental treatments currently underway.

Zarychanski and his team — which started with three scientists, and have grown to a team of 30 — lead two of these international trials from Winnipeg. Formally named the Anti-thrombotic Therapy to Ameliorate Complications of COVID-19 trial (ATTACC) and the Randomized, Embedded, Multifactorial Adaptive Platform (REMAP) study, both study the use of heparin — a blood thinner used to prevent clots — as a therapy for COVID-19, which often results in uncontrolled blood clotting, which can in turn lead to organ failure and death.

The team also co-leads and takes part in two trials that test transferring plasma containing infection-fighting proteins from recovered COVID-19 patients to current patients; and the Solidarity trial, which evaluates COVID-19 treatments on an international level.

Results from Winnipeg-led trials is merged with international data and used by physicians to learn what treatments are working across the world — a patient here could inform treatment in Turkey, a patient in Brazil could inform treatment of someone here — and continues to grow in scope. Work done by Zarychanski’s team has been integrated into trials internationally, and there are currently more than 2,000 patients in the ATTACC and REMAP trials around the world.

“I think that it’s comforting to know that you don’t have to just hope for the best and get a comfortable bed and oxygen, that there are therapies,” he said. “And their participation could help save their life, but also will help save lives around the world.”

There’s about a 50 per cent chance that someone who agrees to be part of trials will actually receive the treatment they sign up for, based on a computer allocation. If they sign up for multiple treatments, it increases their chances at getting at least one. If they are part of the group that doesn’t receive an experimental treatment, they receive the current standard of care. In this way, scientists get an unbiased look at the effectiveness and safety of the experimental treatment.

“It’s immune to our emotions, it’s immune to our best intentions: the data at the end of the day will speak for itself,” Zarychanski said.

The trial process has been proven to work. The current standard of care includes the use of corticosteroids, which was proven through clinical trials to reduce mortality in COVID-19 patients by as much as 12 per cent.

“That is incredible,” he said. “All those people, that 12 per cent difference, got to go home and see their husband again, or wife, or kids.”

Zarychanski also co-led the Canadian arm of a study that eventually dismissed hydroxychloroquine, a treatment lauded by U.S. President Donald Trump without evidence, after a proper clinical trial proved it made no difference in the prevention or treatment of COVID-19.

‘We’re… likely to change the face of clinical research forever, and it’s come out of Manitoba’– critical-care physician and researcher Ryan Zarychanski

He bristled when discussing the current standard of experimental treatment in the United States, where thousands of Americans have received convalescent plasma as a treatment, for example, at a cost he estimates as “probably billions,” without a clinical-trial structure similar to the one being used in Canada and much of the rest of the world.

“If they’re right, it’s irresponsible, because the world still doesn’t know if it works,” he said.

“If it didn’t work after 5,000 or 6,000 patients, whatever it took, then the United States could have stopped investing, donors could have stopped donating, and they could have gone on with their lives and re-invested their time, energy and resources into finding an effective therapeutic. Totally irresponsible. It’s actually even indefensible, the strategy taken.”

Our southern neighbour has found itself an outlier, Zarychanski suggested, owing to pressure put on the U.S. Food and Drug Administration by the current leadership.

“It’s a supreme person having total authority in the setting of a re-election year,” he said.

COVID-19 has changed nearly every aspect of health-care administration, some temporarily, others permanently, and the shift to clinical trials becoming integrated into day-to-day healthcare is a new process Zarychanski hopes will become standard.

Zarychanski’s team is working to move the province to a system where clinical research is embedded into clinical care, but that transition has occurred slowly, and reflects a cultural shift in the way health care is provided — in that regard, he said, COVID-19 has provided a “wedge opportunity” to show Manitobans a learning health system.

“It was a great time to launch, in the setting of COVID, because we had no other therapies. If we were doing things typically, where we carefully plan trials, we launch them slowly and deliberately, get people on board, it can take years,” he said.

“Or we could say, ‘Look, we don’t know what works, but instead of throwing drugs that may or may not work in a setting of people’s emotions and best intentions, we’re going to embed clinical trials into clinical care.’”

Nora Choi is used to 12-hour days at this point.

As a research co-ordinator of Manitoba’s COVID-19 clinical trial team, her life was turned upside down in a unique way when the virus hit Manitoba. Previously focused in nursing home research, she joined the clinical-trial team after realizing there was a chance to provide on-the-ground support to patients.

“This is probably, hopefully, a once-in-a-lifetime opportunity,” she joked.

She’s responsible for all COVID-19 admissions at Grace Hospital. First thing in the morning, she checks for updates on the clinical trials underway. Next she checks the intensive care unit to find out which patients are COVID-19 positive and eligible for the clinical trials. Then she speaks with the patient — or their family, if the patient is unable to speak — about participating.

She collects data on their response to treatment and follows up with patients daily, both during their stay and after they’re discharged.

“A lot of screening eligible patients, and a lot of data collection… it’s really great, because everyone’s really willing to help each other out,” she said.

Patients are admitted Monday through Sunday, and as hospitalizations continue to spike, her workload gets more extensive. Long days in full personal protective equipment and direct contact with COVID-19 positive patients are a new reality.

She calls the ordeal “stressful,” but also approaches her position with a cool rationality — the work has to be done, and if someone has to do it, why not her?

“I think someone needs to do the job, and as hard as it is every day, I honestly don’t mind,” she said.

“I know some people are quite afraid of it, but I think the research has to get done.”

Fellow co-ordinator Quinn Tays echoed the sentiment. A chemistry student and researcher, he works with COVID-19 patients at St. Boniface hospital, work he calls “really rewarding.”

“The first few times on the ward are definitely a little jarring, but then I started to realize — it’s just patients that are sick, and getting care like most other hospital wards,” he said.

“There’s always COVID looming at the back of your mind and you’re taking extra precautions, you’re wearing full PPE in there, but it comes down to it just being a hospital ward.”

Tays has never been part of a clinical trial before this, and said he was proud that his first had such a widespread impact.

“Being part of international trials is great,” he said. “We often feel like small-town Manitoba, but it just feels like we’re really representing ourselves and doing our part for science and to fight the pandemic.”

Choi laughs when asked what she plans to do when COVID-19 is more of a distant memory than a constant presence, but the answer also comes quickly: she wants to take some time off.

“Maybe travel a bit; I know that’s been put on hold for most people,” she said. “Just getting back to my regular schedule, having more regular days.”

No matter where the future of COVID-19 treatment goes, Zarychanski stressed, Manitoba will have been on the frontline of it, thanks to researchers such as Tays and Choi.

“It takes a toll on them too — my God, I don’t even know how to thank them enough… it’s exhausting to wear an N95 for 12 hours a day, and they’re doing it every day,” he said.

Zarychanski believes their service, and the work they’ve produced, speaks to a wider cultural attitude among Manitobans.

“We’re big blood donors, we’re big volunteers,” he said. “We’re big contributors when we can in times of need.”

malak.abas@freepress.mb.ca

Twitter: malakabas_