Mortality rates among COVID-19-linked hospitalisations stand at a reported 17.1%,¹ which is markedly above the global COVID-19 mortality rate of 1.3%, as calculated based on the current global data on COVID-19 case load and associated deaths.² Risk of mortality usually increases shortly after intubation, and thus monitoring the treatment impact on both the need for intubation and overall outcomes will better inform future treatment planning.³

Colchicine, an oral anti-inflammatory drug commonly prescribed for gout, is generally safe and cost-effective.⁴ Dexamethasone and tocilizumab, also anti-inflammatory agents although usually prescribed for non-COVID diseases, have shown some success in reducing mortality rates in patients hospitalised for severe COVID-19.^5,6 Numerous trials have explored other drugs that may show similar effects, with a recent trial testing if the addition of colchicine to standard care could reduce mortality or need for intubation.⁷

A recent randomised trial in a total of 1,279 adult patients (mean age of 62 years) with COVID-19 investigated the effect of colchicine in patients who received either standard care (N=639) alone or standard care with colchicine (N=640).⁷ Majority of patients were randomised within the first two days of hospital admission. Approximately two thirds of the study population were male. Most (91.5%) patients received corticosteroids as part of their in-hospital treatment, and many had a history of hypertension (47.7%), and diabetes (22.7%).⁷

Colchicine was administered orally, at a loading dose of 1.5 mg at randomisation, followed by 0.5 mg within 2 hours of initial dose, and a maintenance dose of 0.5 mg twice daily for 14 days or until discharge.⁷

The key findings of the study were as follows⁷:

• At 28-days post randomisation, mechanical ventilation or death occurred in 25.0% of patients in the colchicine group compared to 28.8% in the group receiving standard care alone (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; p=0.08).
• The difference in 28-day mortality rates was not statistically significant (20.5% with colchicine versus 22.2% with standard care alone; HR, 0.88; 95% CI, 0.70-1.12; p=0.30).
• There were no adverse events of notable concern, and diarrhoea was the most frequently reported adverse effect with colchicine (11.3%) compared to 4.5% in the standard care only group.

The trial was powered to detect a risk difference of 27% for the combined effect on 28-day mortality and intubation rates, but only observed a 17% risk difference which was not statistically significant.⁷ However, the observed risk reduction may indicate that addition of colchicine to standard care could potentially result in modest clinical benefits.⁷ With the current findings, the trial has low statistical power (roughly 33%) to detect modest improvement with treatment, thus, data from larger trials are needed to better understand the potential benefits of including colchicine to standard care.⁷ The ongoing ACT trial uses a higher dose of colchicine, however results are yet to be published.⁸

References

1. Macedo A, et al. Ann Epidemiol 2021;57:14-21.
2. Johns Hopkins University COVID-19 Dashboard. Available at: https://coronavirus.jhu.edu/map.html. Accessed 7 March 2022.
3. Nishikimi M, et al. Sci Rep 2021;11:21124.
4. Tardif JC, et al. N Engl J Med 2019;381:2497-2505.
5. Horby P, et al. N Engl J Med 2021;384:693-704.
6. Ghosn L, et al. Cochrane Database Syst Rev 2021;3:CD013881.
7. Diaz R, et al. JAMA Netw Open 2021;4:e2141328.
8. S. National Library of Medicine ClinicalTrials.gov. Available at: https://www.clinicaltrials.gov/ct2/show/NCT04324463. Accessed 7 March 2022.