AIMS: We aimed to perform a meta-analysis of randomized trials investigating the effect of colchicine in patients with COVID-19.
MATERIALS & METHODS: We systematically searched electronic databases and clinical trial registries (up to October 17, 2021) for eligible studies. The outcomes of interest were all-cause mortality and duration of hospital stay. Meta-analysis with the random-effects model was used to estimate the pooled odds ratio (OR) of mortality and 95% confidence interval (CI). The pooled standardized mean difference of duration of hospital stay with 95% CI between colchicine users and non-colchicine users was estimated using Cohen's d index.
RESULTS: The meta-analyses revealed no significant difference in the odds of mortality (pooled OR = 0.76; 95% CI: 0.53-1.07), but a significant reduction in the duration of hospital stay with the use of colchicine (pooled standardized mean difference = -0.59; 95% CI: -1.06 to -0.13).
DISCUSSION AND CONCLUSION: The ability of colchicine to reduce the length of stay in hospitalized patients with COVID-19 is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. Nevertheless, such beneficial effects of colchicine did not translate into mortality benefits in patients with COVID-19.
METHODS: This is a systematic review and a meta-analysis evaluating the evidence from clinical trials on the effect of colchicine and corticosteroids against COVID-19. In this review, we have systematically searched five databases [(PubMed, Embase, clinicaltrials.gov, ICTRP, CINAHL (EBSCO)]. Cochrane's data extraction sheet was used to collect the required information, and RevMan-5.4.1 was used to conduct the meta-analysis and to assess the risk of bias. The review was registered in Prospero (CRD42022299718).
RESULTS: The total number of included studies was 17, with 18,956 participants; the majority were male 12,001. Out of which, 8772 participants were on colchicine, 569 took methylprednisolone, and 64 patients received prednisolone. The meta-analysis has shown that colchicine had no significant effect on reducing the mortality rate among COVID-19 patients [OR 0.98(95% CI 0.90-1.08), p = .70), I2:1%)], corticosteroids have significantly reduced the mortality rates [OR 0.55 (95% CI 0.33-0.91), p = .02, I2:40]. Colchicine did not reduce the incidence of ICU admissions [OR 0.74 (95% CI 0.39-1.40), p = .35, I2:0%], while steroidal drugs significantly reduced the ICU admissions [OR 0.42 (95% CI 0.23-0.78), p = .005, I2:0%]. Unlike steroidal drugs [OR 0.53 (95% CI 0.30-0.95), p = .03, I2:61%], colchicine failed to reduce the need for mechanical ventilation [OR 0.73 (95% CI 0.48-1.10), p = .13, I2:76%]. Steroidal drugs significantly reduced the duration of hospitalization among COVID-19 patients [OR -0.50 (95% CI -0.79-0.21), p = .0007, I2:36%].
CONCLUSIONS: The use of colchicine did not significantly reduce the mortality rate, ICU admissions, and mechanical ventilation among COVID-19 patients. Conversely, corticosteroids significantly reduced the mortality rate, ICU admissions, mechanical ventilation, and hospitalization duration among COVID-19 patients.
METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023.
CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.
Methods: Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats' back skin.
Results: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel.
Conclusion: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.