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The oral, anti-inflammatory drug colchicine can prevent complications and hospitalizations in nonhospitalized patients newly diagnosed with COVID-19, according to a press release from the ColCORONA trial investigators.
After 1 month of therapy, there was a 21% risk reduction in the primary composite endpoint of death or hospitalizations that missed statistical significance, compared with placebo among 4488 outpatients enrolled in the global, phase 3 trial.
After excluding 329 patients without a confirmatory PCR test, however, the use of colchicine was reported to significantly reduce hospitalizations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%.
“We believe that this is a medical breakthrough. There’s no approved therapy to prevent complications of COVID-19 in outpatients, to prevent them from reaching the hospital,” lead investigator Jean-Claude Tardif, MD, from the Montreal Heart Institute in Quebec, Canada, told theheart.org | Medscape Cardiology.
“I know that several countries will be reviewing the data very rapidly and that Greece approved it today,” he said. “So this is providing hope for patients.”
Having been burned by hydroxychloroquine and other treatments brought forth without peer review, the response to the announcement was tempered by a desire for more details.
Asked for comment, Steven E. Nissen, MD, Cleveland Clinic Foundation, Cleveland, Ohio, was cautious. “The press release about the trial is vague and lacks details such as hazard ratios, confidence intervals, and P values,” he told theheart.org | Medscape Cardiology.
“It is impossible to evaluate the results of this trial without these details. It is also uncertain how rigorously data were collected,” he added. “We’ll need to see the manuscript to adequately interpret the results.”
The evidence in the press release is hard to interpret, but early intervention with anti-inflammatory therapy has considerable biologic appeal in COVID, said Paul Ridker, MD, MPH, who led the pivotal CANTOS trial of the anti-inflammatory drug canakinumab in the post-MI setting, and is also chair of the ACTIV-4B trial currently investigating anticoagulants and antithrombotics in outpatient COVID.
“Colchicine is both inexpensive and generally well tolerated, and the apparent benefits so far reported are substantial,” Ridker, from Brigham and Women’s Hospital in Boston, Massachusetts, told theheart.org | Medscape Cardiology. “We are eager to see the full data as rapidly as possible.”
The commonly used gout and rheumatic disease agent costs about 26 cents in Canada and between $4 and $6 in the United States. As previously reported, it reduced the time to clinical deterioration and hospital stay but not mortality in the 105-patient Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention (GRECCO-19) study.
Tardif said he’s looking forward to having the data in the public domain and that they acted swiftly because the evidence was “clinically persuasive” and “the health system is congested now.”
“We received the results Friday, January 22 at 5 p.m., an hour later we were in meetings with our data safety monitoring board [DSMB], 2 hours later we issued a press release, and a day later we’re submitting a full manuscript to a major scientific journal, so I don’t know if anyone has done this at this speed,” he said. “So we are actually very proud of what we did.”
ColCORONA was designed to enroll 6000 outpatients, at least 40 years of age, who were diagnosed with COVID-19 infection within the previous 24 hours, and had a least one high-risk criterion, including age at least 70 years, body mass index ≥ 30 kg/m2, diabetes mellitus, uncontrolled hypertension, known respiratory disease, heart failure or coronary disease, fever of ≥ 38.4°C within the last 48 hours, dyspnea at presentation, bicytopenia, pancytopenia, or the combination of high neutrophil count and low lymphocyte count.
Participants were randomly assigned to receive either placebo or colchicine 0.5 mg twice daily for 3 days and then once daily for another 27 days.
The number needed to prevent one COVID-19 complication is about 60 patients, Tardif said.
Colchicine was well-tolerated and resulted in fewer serious adverse events than with placebo, he said. Diarrhea occurred more often with colchicine, but there was no increase in pneumonia. Caution should be used, however, in treating patients with severe renal disease.
Tardif said he would not prescribe colchicine to an 18-year-old COVID outpatient who doesn’t have any concomitant diseases, but would for those meeting the study protocol.
“As long as a patient appears to me to be at risk of a complication, I would prescribe it, without a doubt,” he said. “I can tell you that when we held the meeting with the DSMB Friday evening, I actually put each member on the spot and asked them, ‘If it were you — not even treating a patient, but if you had COVID today, would you take it based on the data you’ve seen?’ and all of the DSMB members said they would.
“So we’ll have that debate in the public domain when the paper is out, but I believe most physicians will use it to treat their patients.”
The trial was coordinated by the Montreal Heart Institute and funded by the Government of Quebec; the National Heart, Lung, and Blood Institute of the US National Institutes of Health; Montreal philanthropist Sophie Desmarais; and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators.