COLCORONA trial: Is gout-drug colchicine set to be the next Ivermectin?

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An unpublished international clinical trial claims “clinically persuasive” evidence of the efficacy of the gout-drug colchicine to treat COVID-19, writes MedicalBrief. Compared to placebo, it reduced hospitalisations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%.

It is being predicted by researchers and doctors that given the continuing ferocity of the pandemic, that there will inevitably be widespread unauthorised re-purposing of colchicine, as is currently the case with Ivermectin and happened also with hydroxychloroquine.

The Montreal Heart Institute (MHI) says the result obtained for the global study population of 4,488 patients “approached statistical significance”. The analysis of the 4,159 patients in whom the diagnosis of COVID-19 was proven by a naso-pharyngeal PCR test has shown that the use of colchicine was associated with “statistically significant reductions in the risk of death or hospitalisation compared to placebo”.

The trial showed that colchicine was “the only effective oral medication yet for treating non-hospitalised patients”, the MHI said in a press release. The study was conducted in Canada, the USSouth Africa, Europe, and South America.

The COLCORONA findings were “very encouraging,” tweeted Prof Martin Landray, of the Big Data Institute at the University of Oxford, in a MedPage Today report. His group’s RECOVERY trial has already randomised more than 6,500 hospitalised patients to colchicine versus usual care as one of the arms of the platform trial, though he did not offer any findings from that study. A small open-label, randomised trial from Greece had also shown less clinical status deterioration in hospitalised patients on colchicine.


However, reports StatNews, not everyone is convinced
. “Outside experts said the data provided were too limited to draw conclusions, leading to discussions of the risks of conducting science via press release, instead of in more detailed manuscripts in peer-reviewed journals. All hoped that colchicine, a cheap and globally available generic medicine with manageable side effects, would prove to be beneficial.”

“No one is going to jump to conclusions when someone says something approaches statistical significance and you can’t see the data,” said Craig Spencer, director of global health in emergency medicine at New York-Presbyterian/Columbia University Medical Centre, “That would be huge, it would be wonderful, but I need more — we all need a little bit more.”

Outside experts view those results as less trustworthy because the trial did not meet its main goal. They also agreed that the number of patients who needed mechanical ventilation or who died is likely to be small, making it difficult to draw firm conclusions.

 

A South African practitioner, who did not want to be named, told MedicalBrief that it was likely that lack of vaccine access and a frantic public demand for a preventive would likely lead to many now trying to access colchine for off-label use, as has been the case with Ivermectin. “Until vaccines are rolled out to substantial levels, the public will make its own arrangements to repurpose low-risk medicines intended for other uses, no matter what the health regulatory authorities decree”. A medical scientist said the regulatory authorities should “butt out” of the treatment decisions of clinicians.

 

MedPage Today reported warnings by some North American physicians about the potential for misuse of the findings. Dr Dhruv Nayyar, of the University of Toronto, tweeted that he has already had “patients inquiring why we are not starting colchicine for them. Science by press release puts us in a difficult position while providing care. I just want to see the data.”

Dr Angela Rasmussen, a virologist with the Georgetown Center for Global Health Science and Security’s Viral Emergence Research Initiative in Washington, agreed: “We don’t need people self-medicating with colchicine.”

Dr Richard Kovacs, immediate past-president of the American College of Cardiology, said that as had bee the case with hydroxychloroquine before research proved little efficacy in COVID-19, “We always get concerned when these drugs are repurposed that we might see an unintended run on the drug and lessen the supply.”

The MHI said in its release that ” in these patients with a proven diagnosis of COVID-19, colchicine reduced hospitalisations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%. This major scientific discovery makes colchicine the world’s first oral drug that could be used to treat non-hospitalised patients with COVID-19.”

“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” said Dr Jean-Claude Tardif, director of the MHI Research Centre, professor of medicine at the Université de Montréal and principal investigator of the COLCORONA trial. “We are pleased to offer the first oral medication in the world whose use could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.”

Treating patients at risk of complications with colchicine as soon as the diagnosis of COVID-19 is confirmed by PCR reduces their risk of developing a severe form of the disease and, consequently, reduces the number of hospitalisations. Prescribing colchicine to patients could help alleviate the problems of hospital congestion and reduce healthcare costs here and around the world.

COLCORONA is a contact-less, randomised, double-blind, placebo-controlled clinical trial that took place at home. It has been conducted in Canada, the US, Europe, South America and South Africa. It was designed to determine whether colchicine could reduce the risk of severe complications associated with COVID-19. COLCORONA was conducted among approximately 4,500 COVID-19 patients not hospitalised at the time of enrolment, with at least one risk factor for COVID-19 complications.

This is the world’s largest study testing an orally administered drug in non-hospitalised patients with COVID-19. The full data have not yet been released.

COLCORONA was co-ordinated by the Montreal Heart Institute’s Montreal Health Innovations Coordinating Centre (MHICC), and funded by the government of Quebec, the National Heart, Lung, and Blood Institute of the US National Institutes of Health (NIH), Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator, an initiative launched by the Bill & Melinda Gates Foundation, Wellcome and Mastercard. CGI, Dacima and Pharmascience of Montreal were also collaborators in the trial.

 

In 2019, the same Montreal Heart Institute researchers published a study showing that colchicine, which is thought to quell inflammation and the immune response, may benefit patients who have had heart attacks, in part by preventing return hospital visits. The researchers began their COVID-19 study of colchicine in March, just as the pandemic was beginning to hit North America.

 

2019 Study details
Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction

Jean-Claude Tardif, Simon Kouz, David D Waters, Olivier F Bertrand, Rafael Diaz, Aldo P Maggioni, Fausto J Pinto, Reda Ibrahim, Habib Gamra, Ghassan S Kiwan, Colin Berry, José López-Sendón, Petr Ostadal, Wolfgang Koenig, Denis Angoulvant, Jean C Grégoire, Marc-André Lavoie, Marie-Pierre Dubé, David Rhainds, Mylène Provencher, Lucie Blondeau, Andreas Orfanos, Philippe L L’Allier, Marie-Claude Guertin, François Roubille,

Publsihed in NEJM on 26 December 2019

Abstract
Background
Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.
Methods
We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.
Results
A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P=0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P=0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P=0.03).
Conclusions
Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo

 

 

Montreal Heart Institute press release

 

Full Stat News report (Open access)

 

2019 MedPage Today (Open access)

 

2019 NEJM study (Open access)

 

 

See also from the MedicalBrief archives:

 

Fact File: Making sense of the Ivermectin controversy

 

Exotics hog the headlines but its an old workhorse that has done the COVID-19 job

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