Efficacy of colchicine in non-hospitalized patients with Covid-19 (pre-print)

Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.

Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.

Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).

Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

Read here (Medrxiv, Jan 26, 2021)

‘Major breakthrough’ | Large study shows effectiveness of colchicine to treat Covid-19

‘A large study launched last March by the Montreal Heart Institute allows a “major breakthrough” in the treatment of COVID-19. Its results show that the anti-inflammatory drug colchicine is effective in treating the disease and preventing its complications. It is the first oral medicine proven to be effective in treating patients before they are admitted to hospital. “We have just provided the planet with hope, exclaims the D.r Jean-Claude Tardif, principal investigator of the COLCORONA study and director of the research center of the Montreal Heart Institute (ICM). We finally have a first treatment that can help patients with COVID before their hospitalization to prevent hospitalizations, prevent intubations and prevent death. ”

‘In 4,159 patients proven to be diagnosed with COVID-19 using a PCR test, colchicine resulted in a 25% decrease in hospitalizations, a 50% decrease in the use of ventilation and a decrease in deaths by 44%. “It’s a major breakthrough,” says Dr Tradif. Colchicine works to prevent the “major inflammatory storm” that affects the lungs and can send patients to hospital.’

Read here (The Canadian, Jan 23, 2021)

Anti-inflammatory therapy for Covid-19 infection: The case for colchicine [also used for gout]

‘Given the large body of data demonstrating colchicine’s inhibitory effects on neutrophil activity, cytokine generation and the inflammation/thrombosis interface, together with an overall lack of evidence for systemic immunosuppression, there is a rationale to study colchicine as a potential treatment for COVID-19. Given that colchicine is generally well tolerated, simple to take and inexpensive, demonstration of colchicine as a useful agent in COVID-19 would potentially spare patients morbidity and mortality, help to conserve valuable clinical resources (hospital floor and ICU beds, ventilators, etc), and dramatically reduce the cost of COVID-19 care. Colchicine might be of particular use in resource-poor rural and developing world settings, both of which have been increasingly affected by COVID-19. However, unless and until evidence is obtained from adequately designed and randomised placebo-controlled trials, this hypothesis must remain speculative.

‘The optimal dose of colchicine for daily use, even in well-established conditions such as gout, is unknown. Many but not all patients tolerate up to 1.2 mg daily in divided doses; whether lower doses such as 0.5 mg or less daily can be equally effective is unknown. The largest colchicine study for COVID-19 (ColCorona) is testing a dose of 0.5 mg daily based on prior cardiology trials. The duration of colchicine therapy for SARS-COV2 infection would also need to be determined. Most studies to date test a treatment duration of 2–4 weeks, concordant with the acute course of the infection; whether a shorter or longer treatment would be optimal is unknown. Finally, the timing of colchicine initiation is uncertain, with some studies beginning treatment in the outpatient setting, and others in the early inpatient setting. Given the recent track record of failure of treatment of severe COVID-19 treatment with anti-IL-6 biologics such as tocilizumab (a much more potent but also more specific immunosuppressive agent), it is likely that the severe inpatient setting is not the optimal condition under which to assess colchicine efficacy.’

Read here (BMJ, Dec 8, 2020)

Hadassah doctors crack the cause of fatal corona blood clots

‘A research team at Hadassah-University Medical Center in Jerusalem’s Ein Kerem discovered that patients who form fatal blood clots have an increased level of alpha defensin protein in their blood... They also say they have a way to treat the cause before it’s too late... At least 30% of patients with coronavirus develop blood clots that block the flow of blood to their kidneys, heart and brain, as well as the lungs, according to international research...

‘Dr. Abd Alrauf Higavi said his team are en route to a solution: administering the drug colchicine to coronavirus patients. Colchicine is an approved drug used in the prevention and treatment of gout attacks, caused by too much uric acid in the blood. Higavi said they have completed testing colchicine on mice and found that it successfully inhibited the release of alpha defensin. Now, they are waiting for the necessary approvals to test it on human coronavirus patients.’

Read here (Jerusalem Post, June 16, 2020)