A press release from a Canadian research group has raised hopes that treating people newly diagnosed with Covid-19 with colchicine, a drug commonly used to treat gout, risks hospitalization can be reduced.
But outside experts said the data given were too limited to draw conclusions, leading to discussions of the risks of conducting science via press release, rather than in more detailed manuscripts in peer-reviewed journals. Everyone was hoping that colchicine, an inexpensive and globally available generic drug with manageable side effects, would be beneficial.
“I’m not, ‘Oh, I’m not buying it,'” said Ashish Jha, dean of the Brown University School of Public Health. “It is possible. There is enough credibility here. It could be a true finding, and if it is, it will be great. But this press release does not bring us there.”
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In the release, released late Friday, the Montreal Heart Institute said the hospitalization or mortality rate was 21% lower among patients in its COLCORONA study who received colchicine compared to those randomly assigned to placebo. The study enrolled 4,488 patients.
But here’s a caveat: the press release says these results are not statistically significant, although the numbers are close. When the researchers excluded 329 patients diagnosed with Covid-19 based on family contacts or clinical symptoms but who did not have positive PCR tests, there was a 25% decrease in hospitalization, and the need for mechanical ventilation and deaths were significantly reduced.
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External experts consider the results to be less reliable because the trial did not achieve its main objective. They also agree that the number of patients requiring mechanical ventilation or who have died is likely to be small, making it difficult to draw firm conclusions. The press release does not contain absolute numbers on the number of people admitted to hospital, who had to be placed on ventilators or who died.
“No one is going to conclude if someone says something approaches statistical significance and you can not see the data,” said Craig Spencer, director of Global Health in Emergency Medicine at New York-Presbyterian / Columbia University Medical Center. ‘big, it’s going to be great, but I need more – we all need a little more. ‘
The story of seemingly promising drugs that did not break out, including, best known, the malaria drug hydroxychloroquine, has left many researchers cautious.
“How many therapies seemed to have had promising topline results and look what happened?” says Ethan Weiss, a cardiologist at the University of California, San Francisco. He gave the example of remdesivir, made by Gilead, where test results are considered contradictory. “Let’s see what the actual results look like and then we can have a conversation.”
In 2019, the same researchers from the Montreal Heart Institute published a study showing that colchicine, which is thought to suppress inflammation and the immune response, can benefit patients with heart attacks, in part by preventing hospital visits. These results were published in the New England Journal of Medicine. The researchers began their Covid-19 study on colchicine in March, just as the pandemic began hitting North America hard.
Jean-Claude Tardif, the lead researcher of both the 2019 study and the current one, said that his team believes that it is important to distribute the results quickly, but that they will publish them in a medical journal and also think that it is important to leave. most of the data from the press release.
The press release calls the results ‘clinically convincing’ and Tardif is quoted as saying that colchicine ‘is the world’s first oral medication whose use could have a significant impact on public health and possibly prevent Covid-19 complications for millions of patients.’
Tardif said he rushed – he does not expect to sleep over the weekend – to compile a report of the full data for a medical journal. It is not clear why the magazine publication had to go ahead with a release that did not contain clear numbers. It is more likely to do pharmaceutical businesses, which have a duty to inform investors about events that could potentially move the market.
The COLCORONA trial was funded by governments and philanthropies, including the Government of Quebec; the American National Institute of Heart, Lung and Blood; philanthropist Sophie Desmarais; and the Covid-19 Therapeutics Accelerator, launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard, so there was no obligation to disclose results immediately.
The results were also less detailed than those in some other press releases during the pandemic, including the result of the RECOVERY trial, which showed the effectiveness against Covid-19 of another inexpensive drug, dexamethasone. The press release contains detailed statistical information, and the findings were published in the New England Journal one month later.
“The result is plausible, but it’s so vague – and we do not have many details – that it is very difficult to know how to interpret it,” said Steven Nissen, a cardiologist and clinical trial at the Cleveland Clinic. said.
Nahid Bhadelia, a doctor of infectious diseases at Boston University, also said that she should see the data – and that she does not like science. But she was optimistic. “I think it makes sense,” she said. “We need to see the data, but it fits the picture that SARS-CoV-2 leads to a kind of congenital immune dysfunction.”
The study, originally planned to run until March 2021, was designed to enroll 6,000 inpatients who were not admitted to the hospital, who would be randomly assigned to receive half a milligram of colchicine twice daily for three days , followed by once a day. dose or a placebo for 27 days. Neither researchers nor the patients knew in which group a patient is. The patients had just been diagnosed and were not admitted to the hospital, which was a disease earlier than most other studies. All were over 40, and each had at least one risk factor for developing severe Covid-19.
It is possible to make trained guesses about the results. Tardif said about 5% of patients were admitted to the hospital. Results with 225 or 250 patients admitted to the hospital – meaning that about 30 hospitalizations were prevented – seem to generally agree with the results described in the release. David Boulware of the University of Minnesota, an infectious disease scientist, calls it “an important step forward, but not a leap.”
Eric Topol of the Scripps Research Translational Institute emailed me that although ‘many data points are missing’, the potential of early therapy would be ‘welcome’, as the only similar treatments are monoclonal antibodies that must be given intravenously. become and ‘rare’ is not getting used to. ”
The decision to stop the trial earlier than expected was taken, Tardif said, because to wait would have meant months of waiting when the drug could now be useful to patients. He said that when the data security and monitoring board, a panel of outside experts monitoring the trial, met Friday night, he asked them if they thought the results were convincing and if they were a patient or a family member. who were diagnosed with Covid-19 would advise. to take colchicine. Everyone said yes.
The story was confirmed by Marc Pfeffer, the Dzau professor of medicine at Harvard Medical School, who is a member of the board’s data security and monitoring board. Pfeffer said he was convinced that colchicine was safe, although it did have side effects. In the NEJM report on its usefulness for people with heart disease, those taking colchicine were more likely to have diarrhea and develop pneumonia.
Pfeffer praised Tardif’s group for succeeding in conducting a large randomized study in patients who were not admitted to the hospital, something others struggled to do. He said the data was generally convincing.
“I think the results are clinically convincing, and I’m sorry you do not have the results to see it,” Pfeffer said. “But you will soon.”
There are also other studies testing colchicine, including part of the RECOVERY trial, which evaluates the drug in sicker patients.