Oral colchicine reduces hospitalisation in international randomised phase 3 outpatient study

Top-line results from a large randomised phase 3 study report clinical benefits from the antiinflammatory drug colchicine and reduced mortality. This is an oral drug used that was studied in outpatients. [1, 2]

The ColCorona study randomised 4488 adults (>40 years old) with PCR-confirmed COVID-19 or clinical criteria, to either oral colchicine (0.5 mg twice daily for three days, then daily for 27 days) or placebo. This was a contactless study, with consultations by phone.

The study included prespecified interim ITT analysis after 25%, 50% and 75% of the planned 6000 participants reached 30-day of follow-up. After the 75% analysis the study Data and Safety Monitoring Board (DSMB) recommended stopping the study – but this was due to practical difficulties of maintaining the call centre during COVID-19 – not from reaching a significant efficacy benefit.

Overall, the composite primary endpoint of death or hospitalisation occurred in 4.7% vs 5.8% of the colchicine and placebo groups respectively: OR 0.79 (95%CI: 0.61 to 1.03), p=0.08.

However, this became significant in the analysis of the 4159 participants with PCR-confirmed COVID-19: OR 0.75 (95%CI: 0.57 to 0.99), p=0.04. Events occurred in 4.5% vs 6.0% of the active vs placebo groups, respectively, and the colchicine group had a 25% risk reduction in the primary endpoint.

Although the press release reported that hospitalisation was reduced by 25%, mechanical ventilation by 50% and death by 44%, only hospitalisation results were statistically significant, with confidence intervals for ventilation and death crossing 1.0.

Significantly fewer serious adverse events were reported in colchicine arm: 4.9% vs 6.3%, p=0.05, with pneumonia in 2.9% vs 4.1%, p=0.02, respectively. Diarrhoea was more frequently reported with colchicine: 13.7% vs 7.3%, p<0.0001.

These results, were first published in a press release from the Montreal Heart Institute (MHI) that led this international study, with sites in Canada, the US, Brazil, South Africa and Spain. However, the pre-review paper was also published online soon after.

Colchicine is an inexpensive medicine commonly used to treat gout and rheumatic disease.

Comment

Shortly after this report was posted, the pre-review paper from this study was loaded online. This review has been updated to include additional details from the paper. [4]

Based on the approximate 7% rate in the paper, the number needed to treat (NNTT) to prevent one hospitalisation would be approximately 85. This might still be effective though as the NNTT is driven more by the low hospitalisation rate rather than low efficacy.

Although diarrhoea is significantly higher with colchicine and might easily be self managed with imodium, there were also significantly higher numbers of pulmonary embolism: 11 (0.5%) vs 2 (0.1%), p=0.01.

However, the paper also describes an urgency to report early results after the study was stopped early. Although 75% of the planned 6000 participants had reached 30 days follow-up, the difference by ITT analysis at this point was not statistically significant.