Please see the bottom of the page with the most recent update to the colchicine literature in COVID-19. This post covers the GRECCO-19, and COLCORONA, and RECOVERY Trials.
I have mentioned this many times before, I like readily available, inexpensive medications such as dexamethasone and colchicine to treat our COVID patients. In this case, the authors are looking at Colchicine. I covered dexamethasone and the RECOVERY trial HERE. For the sake of sexy trial names, this study goes by GRECCO-19. As you can imagine, it was performed in Greece. This study is from June 24, 2020.
The following is my opinion from what I’ve seen. Others have said the same but I haven’t read substantial data on it. COVID has two waves. The acute viral illness phase and the cytokine storm phase. The first phase is when you feel crummy and the second is when your body tries to kill you. Not everyone progresses to the second phase, thankfully. What differentiates a person developing cytokine storm is still unknown. Our job is to mitigate how much they actually storm. This is the reason why I personally have been providing my patients with corticosteroids from day one. Anti-IL-6 medications such as tocilizumab have also had promising results. Corticosteroids are cheap. Tocilizumab is not. In this case, the authors were investigating using colchicine as the anti-inflammatory agent. These patients are NOT ICU patients.
Quick Colchicine background
Colchicine is possibly in the shelf of your parent or grandparent who has gout. Cardiologists also like to provide this medication to patients who have pericarditis. The scope of this post does not include a deep dive into this medication. It is an anti-inflammatory medication that does not shred the kidneys like NSAIDs do. I am extremely hesitant to administer any NSAIDs in my ICU patients for those reasons. The safety profile includes mostly GI issues such as diarrhea and vomiting. As you can expect, in this trial the patients receiving colchicine had far more diarrhea with a number needed to treat (NNT) of just 3.6.
Study details for GRECCO-19 (Updated 06/28/20)
Prospective, open-label, randomized clinical trial. 1:1 colchicine or control group. You have all the limitations of it being open label. The trial took place in April 2020. By that time we already had a little bit of experience taking care of these patients. They enrolled 105 patients. 55 in the colchicine group and 50 in the control arm.
A confounder here is that the vast majority of patients received chloroquine or hydroxychloroquine and azithromycin.
Colchicine Dose Used in the GRECCO-19 Trial
1.5mg loading dose followed by 0.5mg 60 minutes after. Patients received 0.5mg twice daily thereafter for up until hospital discharge or up to three weeks.
For some background, when patients have gout, they get 1.2 mg initially followed by 0.6 mg every hour for 6 hours or until their GI symptoms start acting up.
End Points of Colchicine in COVID
1. maximum high-sensitivity cardiac troponin level
2. time for C-reactive protein to reach more than 3 times the upper reference limit
3. time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death.
1. the percentage of participants requiring mechanical ventilation
2. all-cause mortality
3. number, type, severity, and seriousness of adverse events
Results (Real World Outcomes) to be seen by giving Colchicine in COVID
There’s no difference in all the fancy biomarkers except for maximum d-dimer (p=0.04). CRP was lower but it wasn’t statistically significant. More than anything, they were looking for an effect on myocardial injury and they didn’t find it.
The cumulative 10-day survival was 83% in the control arm and 97% in the colchicine arm (NNT= 7.1). We need to take into account the limitations of this, of course, but in the absence of harm outside of some GI issues, it’s worth considering.
In the control group 5 patients needed intubation and 3 of those died.
In the colchicine group only 1 patient needed intubation and they died.
Wrapping it up
Will I be using colchicine in my patients? Short answer is no. There’s no data for ICU vented patients. Those patients will be on dexamethasone. Could I potentially combine the dexamethasone and colchicine? Yes. I don’t see any interactions but I cannot recommend that as this is all off-label use with all the limitations that accompany that.
Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinèz-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195; PMCID: PMC7315286.
Link to FULL FREE Article
Check out this post on my podcast!
Colchicine for Outpatient COVID-19: COLCORNA Trial (Updated 01/28/21)
Just yesterday (01/27/21) there is a pre-peer reviewed article on culture scene in outpatients who have COVID-19. I have to state that this is not peer reviewed and therefore one cannot change your practice based on the study at this moment. Expectations are that it will be peer reviewed in the upcoming days or weeks. I had to give the disclaimer that I am not an outpatient doctor and I do not take care of COVID-19 patients in the ambulatory setting. I am a critical care doctor. I must also get the disclaimer that I am excited about a potential therapy that could keep patients from coming into the hospital and eventually deteriorating to the point where they need my care in the intensive care unit.
Before we begin discussing this paper that was published on 21 January of 2021 I must tip my hat to the authors for doing a fantastic job of enrolling these many patients in an outpatient study. Personally, I have not seen an outpatient study this robust in COVID-19 as sorely needed as it is.
Those of us who are in the inpatient and ICU setting know that the main complication of COVID-19 is this hyper inflammatory state as well as his hypercoagulable state that some patients eventually hit. Unfortunately, we do not know the exact rationale as to why people hit either of these two manifestations clinically. This is the postulation behind using dexamethasone as it has an anti-inflammatory properties as well as using anticoagulation to prevent thromboembolic phenomenon and other complications.
The authors were trying to investigate whether culture scene had any clinical effects on complications of COVID-19 which include hospitalization and death. They also wanted to look at the safety and tolerability of this pharmaceutical agent. To be continued regarding Colchicine and COVID.
Link to COLCORONA Article
Link to FULL FREE COLCORONA PDF
Now Peer Reviewed!
Tardif JC, Bouabdallaoui N, L’Allier PL, Gaudet D, Shah B, Pillinger MH, Lopez-Sendon J, da Luz P, Verret L, Audet S, Dupuis J, Denault A, Pelletier M, Tessier PA, Samson S, Fortin D, Tardif JD, Busseuil D, Goulet E, Lacoste C, Dubois A, Joshi AY, Waters DD, Hsue P, Lepor NE, Lesage F, Sainturet N, Roy-Clavel E, Bassevitch Z, Orfanos A, Stamatescu G, Grégoire JC, Busque L, Lavallée C, Hétu PO, Paquette JS, Deftereos SG, Levesque S, Cossette M, Nozza A, Chabot-Blanchet M, Dubé MP, Guertin MC, Boivin G; 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 Aug;9(8):924-932. doi: 10.1016/S2213-2600(21)00222-8. Epub 2021 May 27. PMID: 34051877; PMCID: PMC8159193.
Link to Article
Link to FULL FREE PDF
Colchicine Does Not Work Per RECOVERY Group: Updated 10/29/21
RECOVERY Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med. 2021 Oct 18:S2213-2600(21)00435-5. doi: 10.1016/S2213-2600(21)00435-5. Epub ahead of print. PMID: 34672950; PMCID: PMC8523117.
Link to Article
Link to FULL FREE PDF
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Disclaimer: Although great care has been taken to ensure that the information in this post is accurate, eddyjoe, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom. These are not medical recommendations. Please read the cited peer-reviewed publications for more legitimate resources.
One thought on “Colchicine for COVID-19: GRECCO-19, COLCORONA & RECOVERY”
Asymptomatic transmission of COVID 19 has been a big concern and the center of much discussion, yet there has been little data on the subject, that I have found. Today this popped into my feed. https://pubmed.ncbi.nlm.nih.gov/32513410/ Thoughts? What have you seen in the research?
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