But some find science-by-press-release troubling.
Anti-inflammatory oral drug colchicine improved COVID-19 outcomes for patients with relatively mild cases, according to certain topline results from the COLCORONA trial announced in a brief press release.
Overall, the drug used for gout and rheumatic diseases reduced risk of death or hospitalizations by 21% versus placebo, which “approached statistical significance.”
However, there was a significant effect among the 4,159 of 4,488 patients who had their diagnosis of COVID-19 confirmed by a positive PCR test:
- 25% fewer hospitalizations
- 50% less need for mechanical ventilation
- 44% fewer deaths
If full data confirm the topline claims — the press release offered no other details, and did not mention plans for publication or conference presentation — colchicine would become the first oral drug proven to benefit non-hospitalized patients with COVID-19.
“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” principal investigator Jean-Claude Tardif, MD, of the Montreal Heart Institute, said in the press release. He predicted its use “could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.”
Currently, the “tiny list of outpatient therapies that work” for COVID-19 includes convalescent plasma and monoclonal antibodies, which “are logistically challenging (require infusions, must be started very early after symptom onset),” tweeted Ilan Schwartz, MD, PhD, an infectious diseases researcher at the University of Alberta in Edmonton.
The COLCORONA findings were “very encouraging,” tweeted Martin Landray, MB ChB, PhD, of the Big Data Institute at the University of Oxford in England. His group’s RECOVERY trial has already randomized more than 6,500 hospitalized patients to colchicine versus usual care as one of the arms of the platform trial, though he did not offer any findings from that study.
“Different stage of disease so remains an important question,” he tweeted. “Maybe old drugs can learn new tricks!” Landray added, pointing to dexamethasone.
A small open-label, randomized trial from Greece had also shown less clinical status deterioration in hospitalized patients on colchicine.
“I think this is an exciting time. Many groups have been pursuing lots of different questions related to COVID and its complications,” commented Richard Kovacs, MD, immediate past-president of the American College of Cardiology. “We’re now beginning to see the fruit of those studies.”
The COLCORONA announcement came late Friday, following closely on the heels of the topline results from the ACTIVE-4a, REMAP-CAP, and ATTACC trials showing a significant morbidity and mortality advantage to therapeutic-dose anticoagulation in non-ICU patients in the hospital for COVID-19.
COLCORONA was conducted remotely, without in-person contact, with participants across Canada, the U.S., Europe, South America, and South Africa. It randomized participants double-blind to colchicine 0.5 mg or a matching placebo twice daily for the first 3 days and then once daily for the last 27 days.
Participants were ages 40 and older, not hospitalized at the time of enrollment, and had at least one risk factor for COVID-19 complications: age 70-plus, obesity, diabetes, uncontrolled hypertension, known asthma or chronic obstructive pulmonary disease, known heart failure, known coronary disease, fever of ≥38.4°C (101.12°F) within the last 48 hours, dyspnea at presentation, or certain blood cell abnormalities.
It had been planned as a 6,000-patient trial, but whether it was stopped for efficacy at a preplanned interim analysis or for some other reason was not spelled out in the press release. Whether the PCR-positive subgroup was preplanned also wasn’t clear. Key details such as confidence intervals, adverse effects, and subgroup results were omitted as well.
While a full manuscript is reportedly underway, “we don’t know enough to bring this into practice yet,” argued Kovacs.
Some physicians also warned about the potential for misuse of the findings and attendant risks.
Dhruv Nayyar, MD, of the University of Toronto, tweeted that he has already had “patients inquiring why we are not starting colchicine for them. Science by press release puts us in a difficult position while providing care. I just want to see the data.”
Angela Rasmussen, MD, a virologist with the Georgetown Center for Global Health Science and Security’s Viral Emergence Research Initiative in Washington, agreed, tweeting: “When HCQ [hydroxychloroquine] was promoted without solid data, there was at least one death from an overdose. We don’t need people self-medicating with colchicine.”
As was the case with hydroxychloroquine before the papers proved little efficacy in COVID-19, Kovacs told MedPage Today: “We always get concerned when these drugs are repurposed that we might see an unintended run on the drug and lessen the supply.”
Citing the well-known diarrheal side effect of colchicine, infectious diseases specialist Edsel Salvana, MD, of the University of Pittsburgh and University of the Philippines in Manila, tweeted a plea for use only in the trial-proven patient population with confirmed COVID-19 — not prophylaxis.
The dose used was on par with that used in cardiovascular prevention and other indications, so the diarrhea incidence would probably follow the roughly 10% rate seen in the COLCOT trial, Kovacs suggested.
In the clinic, too, there are some cautions. As Elin Roddy, MD, a respiratory physician at Shrewsbury and Telford Hospital NHS Trust in England, tweeted: “Lots of drug interactions with colchicine potentially — statins, macrolides, diltiazem — we have literally been running up to the ward to cross off clarithromycin if RECOVERY randomises to colchicine.”