COVID-19 Drugs: International Study Finds Colchicine Effective For Non-Hospitalized COVID-19 Patients
: A new study by researchers from University of Montreal-Canada,New York University-USA, Universidad Autónoma de Madrid-Spain, Universidade de São Paulo-Brazil, Mayo Clinic-USA, San Francisco General Hospital-USA, Cedars-Sinai Heart Institute-USA And Université Laval-Canada has found that the existing anti-inflammatory oral drug drug-Colchicine
could be repurposed to treat non-hospitalized COVID-19 patients.
The study found that the drug could be used to support oral therapy at home as it improved COVID-19 outcomes for patients with relatively mild cases, according to certain topline results from the COLCORONA trial.
The study found that the drug used for gout and rheumatic diseases reduced risk of death or hospitalizations by 21% versus placebo, which "approached statistical significance."
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the prevention of pericarditis and familial Mediterranean fever.
Also there was a significant effect among the 4,159 of 4,488 patients who had their diagnosis of COVID-19 confirmed by a positive PCR test:
-25% fewer hospitalizations
-50% less need for mechanical ventilation
-44% fewer deaths
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.01.26.21250494v1
Should the study results be endorsed by a peer review, colchicine could become the first oral drug proven to benefit non-hospitalized patients with COVID-19.
Principal investigator Jean-Claude Tardif, MD, of the Montreal Heart Institute told Thailand Medical News, "Our research shows the efficacy of colchicine treatment in preventing the 'cytokine storm' phenomenon and reducing the complications associated with COVID-19."
Thailand Medical News had already covered the possible use of colchicine to treat COVID-19 as early as April 2020. https://www.thailandmedical.news/news/covid-19-pneumonia-drugs-colchicine-being-studied-to-prevent-cytokine-storms-in-patients
Dr Tardif predicted its use "could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients."
At present the "tiny list of outpatient therapies that work" for COVID-19 includes convalescent pl
asma and monoclonal antibodies, which "are logistically challenging (require infusions, must be started very early after symptom onset)."
This new COLCORONA findings were "very encouraging," said Dr Martin Landray, MB ChB, PhD, of the Big Data Institute at the University of Oxford in England. His group's RECOVERY trial has already randomized more than 6,500 hospitalized 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.
Dr Landray added, pointing to dexamethasone,"Different stage of disease so remains an important question," he tweeted. "Maybe old drugs can learn new tricks!"
Also a small open-label, randomized trial from Greece had also shown less clinical status deterioration in hospitalized patients on colchicine. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593
Dr Richard Kovacs, MD, immediate past-president of the American College of Cardiology commented, "I think this is an exciting time. Many groups have been pursuing lots of different questions related to COVID and its complications. We're now beginning to see the fruit of those studies."
The results of the COLCORONA announcement came late last week, following closely on the heels of the topline results from the ACTIVE-4a, REMAP-CAP, and ATTACC trials showing a significant morbidity and mortality advantage to therapeutic-dose anticoagulation in non-ICU patients in the hospital for COVID-19.
The COLCORONA trial was conducted remotely, without in-person contact, with participants across Canada, the U.S., Europe, South America, and South Africa. It randomized participants double-blind to colchicine 0.5 mg or a matching placebo twice daily for the first 3 days and then once daily for the last 27 days.
Most participants were ages 40 and older, not hospitalized at the time of enrollment, and had at least one risk factor for COVID-19 complications: age 70-plus, obesity, diabetes, uncontrolled hypertension, known asthma or chronic obstructive pulmonary disease, known heart failure, known coronary disease, fever of ≥38.4°C (101.12°F) within the last 48 hours, dyspnea at presentation, or certain blood cell abnormalities.
Initially the COLCORONA trial was planned to enroll 6,000 patients, but it was stopped after about 75% were recruited because of the burden it was creating for site investigators and for central administration.
However it should be noted that despite nearly 4,500 patients enrolled, they experienced too few events to demonstrate a statistically significant benefit for colchicine for most outcomes.
The study findings also covered adverse events in which diarrhea, the most common, was reported about twice as often with colchicine than with placebo (13.7% vs 7.3%). Pneumonia was somewhat less frequent with the active drug. Perhaps most worrisome, 11 patients assigned to colchicine experienced pulmonary embolism versus two in the placebo group.
Dr Kovacs added, "We don't know enough to bring this into practice yet."
The ancient centuries-old drug has long been used for gout and arthritis and more recently for pericarditis along with showing promise in cardiovascular secondary prevention.
The drug is relatively very cheap and is available in most parts of the world.
However some doctors also warned about the potential for misuse of the findings and attendant risks.
Some physicians are already worried however as they already had patients inquiring why doctors are not starting colchicine for them!
Till more data is forthcoming, doctors are still reluctant to prescribe the drug.
One doctor commented,"When HCQ [hydroxychloroquine] was promoted without solid data, there was at least one death from an overdose. We don't need people self-medicating with colchicine."
Also as was the case with hydroxychloroquine before the papers proved little efficacy in COVID-19, Dr Kovacs warned, "We always get concerned when these drugs are repurposed that we might see an unintended run on the drug and lessen the supply."
Also some physicians warned that with the well-known diarrheal side effect of colchicine, the drug should be only used in the trial-proven patient population with confirmed COVID-19 and not as a prophylaxis.
Dr Kovacs suggested that the dose used was on par with that used in cardiovascular prevention and other indications, so the diarrhea incidence would probably follow the roughly 10% rate seen in the COLCOT trial.
It should also be noted that there are lots of drug interactions with colchicine potentially from statins, macrolides, diltiazem and a potential to cross off clarithromycin if RECOVERY randomizes to colchicine.
The effect of colchicine on the primary endpoint was consistent across subgroups of patients based on various clinical characteristics. Although the benefits of colchicine appeared to be more marked in patients with diabetes and men, there was no significant heterogeneity in the results. Because the event rates were higher in patients with these characteristics, the effect of colchicine might have been more readily detectable. Diabetes is a pro-inflammatory state, which might explain the greater risk of complications of COVID-19 in patients afflicted by that disease. Despite the link between weight, insulin resistance and type 2 diabetes, the effects of colchicine did not differ whether the body-mass index was above or below 30 kg per square meter. In contrast, there is no readily obvious basis for a sex-related difference in responses to colchicine. Of note, the concomitant use of an inhibitor of the renin-angiotensin system did not appear to modify the clinical response to colchicine.
The study team concluded that among non-hospitalized patients with confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospitalization than placebo.
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