COLCORONA: Colchicine for COVID-19

Nishma Singhal, James Douketis

Dr Nishma Singhal, associate professor in the Divisions of Infectious Diseases and General Internal Medicine at McMaster University, joins Dr James Douketis to discuss recent updates on colchicine in the outpatient treatment of coronavirus disease (COVID-19).

Tardif JC, Bouabdallaoui N, L'Allier PL, et al; COLCORONA Investigators. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021 May 27:S2213-2600(21)00222-8. doi: 10.1016/S2213-2600(21)00222-8. Epub ahead of print. PMID: 34051877; PMCID: PMC8159193.

For a Publications of the Week article discussing the role of colchicine in outpatient treatment of COVID-19, click here.

James Douketis, MD: Hello, everyone. My name is Jim Douketis and I’m happy to welcome you once again to another edition of the Master Textbook of [Internal] Medicine Paper of the Week, the McMaster Perspective. I’m joined today by Dr Nishma Singhal, associate professor in the Department of Medicine and also an infectious disease consultant at the Hamilton General Hospital. Of course, she’s at McMaster University. Welcome, Nishma.

Nishma Singhal, MD: Thank you. Thanks for having me today.

James Douketis: We’re gonna be talking about the COLCORONA trial. This is yet another study involving patients with COVID-19 who were either diagnosed based on polymerase chain reaction (PCR) testing or clinical criteria and [it] looked to see whether [colchicine] may have had an anti-inflammatory effect to mitigate against some of the downstream complications of COVID-19. So, first off, Nishma, what do you think overall about the trial? Do you think it’s a major practice-changing trial among our patients who have COVID-19?

Nishma Singhal: [It was] certainly one of the biggest trials looking at the use of colchicine. I think it’s important in terms of exploring the different treatment options. One of the things that we’ve been limited on is the outpatient scenario, where there are some monoclonal antibodies, but there is limited utility due to the logistical issues with regard to intravenous infusions, so it’s nice to have some data on something that’s oral, simple, and inexpensive.

I think there are definitely lots of limitations in terms of the criteria, people who were qualified for this trial. So, I don’t [think] that it’s entirely practice changing in terms of the entire population who is getting COVID-19, but I think [that], on a case-by-case basis, it may be a discussion that you want to have with individual patients. For instance, the trial only enrolled people who were >40, who were at risk for more severe illness (so, they had to have underlying comorbidities, such as diabetes, heart disease, respiratory disease) [and those who] were >70 years old. Certainly, it’s not something that we would be using on a widespread basis in the outpatient setting, but it might be something worth exploring on a case-by-case basis in certain individuals.

James Douketis: OK. Well, thanks, that’s a good introduction. Let’s move on to the actual trial itself. It is a very large trial. Can you comment maybe on a few of the strengths and the weaknesses? And, in particular, what did you think about the overall absolute benefit in terms of the numbers here and how that affects... It seems to have an impact on your enthusiasm for the trial. So, maybe you could expand upon those 2 things?

Nishma Singhal: Sure. In terms of design, it was a randomized placebo-controlled trial, so, certainly [I am] not concerned with the design. They did the trial early, I think more for logistical reasons, so they only enrolled about 75% of their initial target. That might be the one limitation. In terms of the actual benefit, as you mentioned at the beginning, they looked at both people who had a clinical as well as PCR-confirmed diagnosis. The majority had PCR-confirmed diagnosis. However, it was only statistically significant in terms of the benefit in those who had a PCR-confirmed diagnosis. So, I think that, especially with diagnostics now being available, we should really focus on that population.

The absolute risk reduction was just >1% —I think there was 1.2%—and that was a composite of hospitalization and death, with the majority of death being driven by hospitalization, which is not surprising, of course. So, the absolute risk reduction in death was 0.2%, [which is] quite minimal from that perspective and obviously not statistically significant when you actually break it down to the individual components because the rate of death was so low. And again, this is a lower-risk population to begin with.

So, I don’t think it’s, as I said, practice changing in that this is the answer to all of our problems with regard to COVID-19 and this is the drug that’s going to prevent anybody from getting really sick. But if there is a high-risk individual who is really concerned, as I said, I think, on a case-by-case basis, exploring... We do know that hospitalization has been a major issue in this pandemic, certainly in Canada and throughout the world, in many, many countries. So, I think it’s not an insignificant endpoint that we need to consider.

However, the absolute risk reduction is quite low and I think that has to be balanced with the potential side effects of colchicine. Certainly, as we know with colchicine, a common side effect—and it can be quite distressing, at least in my personal practice—is obviously diarrhea or gastrointestinal (GI) [symptoms]. Not surprisingly, they saw a significant increase in the GI side effects in this trial as well. So, again, I think that warrants a very detailed discussion with your patients in terms of deciding whether or not they are willing to deal with this side effect of diarrhea.

Again, in this trial, unlike [in] the other small, randomized controlled trials that were done prior to [the] COLCORONA [trial], there actually was a 30-day course, [while] some of the other trials use like a 10-day course. So, it’s not [using the drug] just for a week or 2. We don’t really know if a shorter course would have the same benefits, but it’s actually a 30-day course of colchicine. That also, I think, has implications.

James Douketis: That’s a tremendously comprehensive response. In fact, you stole my thunder for the other questions that I was going to ask you. Any final words for our clinicians out there who are dealing with nonhospitalized COVID-19 patients in terms of just general advice for them?

Nishma Singhal: Yeah, I think one other thing that I’d like to just add is [that] this trial was done in 2020, so we also do not know if colchicine will have the same effect against the variants that we’ve seen emerging. And especially for Canada, given that predominant strains are either the Alpha or the Delta strains that are circulating, it may be a bit difficult to extrapolate [what the exact benefit is]. As I said, I think, having an individualized discussion with your patients if you’re managing individuals in the outpatient setting… I don’t think that this is the magic bullet, but if patients are really concerned... I certainly would advise that, if you’re going to use it, make sure that they actually do fall within the criteria. For someone who’s [at] low risk, I think they’re really just going to get side effects without any benefit. And so, I really would caution against using it in that population for sure.

James Douketis: Really sensible comments. Thank you very much for your insights on the COLCORONA trial and, in general, on management of COVID-19 patients who are not hospitalized. I’m certain we’re gonna hear more about this and, hopefully, we’ll have you back for another review. Dr Nishma Singhal, thank you very much for your assessment and insights.

Nishma Singhal: Thank you once again.

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