Colchicine does not prevent mechanical ventilation or reduce mortality risk in COVID-19 hospitalisations

25 March, 2022

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.