Colchicine treatment in COVID-19: the remaining unsolved question.
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ABSTRACT:
SUBMITTER: Rojas-Villarraga A
PROVIDER: S-EPMC8530469 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC8521385 | biostudies-literature
Project description:ObjectiveTo evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19.DesignThis interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death.Results152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group.ConclusionColchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome.
| S-EPMC9618432 | biostudies-literature
Project description: Not available
| S-EPMC7667946 | biostudies-literature
Project description:Colchicine is widely investigated for cardioprotection of COVID-19 patients since it can prevent the phenomenon of 'cytokine storm' and may reduce the complications arising from COVID-19. Despite the potentially beneficial effects of colchicine, there is no consensus on the appropriate dosage regimen and numerous schemes are currently used.In this study, simulations were performed to identify the ability of dosage regimens to attain plasma levels in CVOID-19 patients, known to be generally safe and efficacious. Since renal and hepatic impairment, as well as, drug-drug interactions have been identified to be the most significant factors increasing colchicine toxicity, the impact of these interactions was assessed in the simulations.Some dosage regimens lead to high colchicine concentrations, while others result in sub-therapeutic levels. Additional dosage schemes were proposed in this study aiming to be applied in patients with clearance insufficiency. Colchicine administration of 0.5 mg twice daily, can be considered safe and effective. In cases of clearance impairment, doses as low as 0.25 mg thrice or twice daily should be applied.Colchicine is a narrow therapeutic index drug and dosage regimens tailored to patients' needs should be designed.
| S-EPMC8054498 | biostudies-literature
Project description:Purpose of Review:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is a pandemic causing havoc globally. Currently, there are no Food and Drug Administration (FDA)-approved drugs to treat COVID-19. In the absence of effective treatment, off-label drug use, in lieu of evidence from published randomized, double-blind, placebo-controlled clinical trials, is common in COVID-19. Although it is vital to treat affected patients with antiviral drugs, there is a knowledge gap regarding the use of anti-inflammatory drugs in these patients. Recent Findings:Colchicine trials to combat inflammation in COVID-19 patients have not received much attention. We await the results of ongoing colchicine randomized controlled trials in COVID-19, evaluating colchicine's efficacy in treating COVID-19. Summary:This review gives a spotlight on colchicine's anti-inflammatory and antiviral properties and why colchicine may help fight COVID-19. This review summarizes colchicine's mechanism of action via the tubulin-colchicine complex. Furthermore, it discussed how colchicine interferes with several inflammatory pathways, including inhibition of neutrophil chemotaxis, adhesion, and mobilization; disruption of superoxide production, inflammasome inhibition, and tumor necrosis factor reduction; and its possible antiviral properties. In addition, colchicine dosing and pharmacokinetics, as well as drug interactions and how they relate to ongoing, colchicine in COVID-19 clinical trials, are examined.
| S-EPMC7367785 | biostudies-literature
Project description:IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta-analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c-reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = -0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = -0.85, p < 0.001). Finally, the D-dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = -0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate-to-severe COVID-19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID-19 treatment.
| S-EPMC8646297 | biostudies-literature
Project description:ObjectiveWe assessed the efficacy of colchicine in COVID-19 patients through a systematic review.MethodsSix databases were searched until March 2022 for studies assessing colchicine versus control in hospitalized patients with COVID-19. The primary outcome was mortality, and secondary outcome was length of hospitalization. Inverse variance and random effect meta-analyses were performed. The strength of evidence was assessed using GRADE.ResultsNine studies (five randomized clinical trials (RCTs) and four non-randomized studies of intervention (NRSI); n = 13,478). Colchicine did not reduce mortality in comparison with the standard of care in RCTs (RR 0.99; 95%CI 0.90 to 1.10; p = 0.90); however, it did reduce mortality in NRSI studies (RR 0.45; 95%CI 0.26 to 0.77; p = 0.02). In the analysis of RCTs, colchicine did not reduce the length of hospitalization in comparison with the standard of care (MD: -2.25 days; 95%CI: -9.34 to 4.84; p = 0.15). Most studies were scored as having a high risk of bias. Quality of evidence was very low for primary and secondary outcomes.ConclusionColchicine did not reduce the mortality and length of hospitalization in comparison with the standard of care in hospitalized patients with COVID-19. The published evidence is insufficient and of very low quality to recommend treatment in patients with COVID-19.
| S-EPMC9105993 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2/novel coronavirus-19 (COVID-19) has rapidly become a global pandemic since the first cases from Wuhan, China, were reported in December 2019. The pandemic has made it more challenging to treat various gastrointestinal disorders, including acute alcoholic hepatitis (AH). One of the mainstays of treatment for severe AH involves corticosteroids (mainly prednisolone). A concern when treating with prednisolone is the worsening of underlying infection. There may be an additional risk in treating COVID-19-infected patients. We present a case of a patient with severe acute AH and concomitant COVID-19 infection who did well with corticosteroid therapy without evidence for worsening infection.
| S-EPMC8483816 | biostudies-literature
Project description:BackgroundColchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated.ObjectiveTo address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19.DesignWe conducted a triple-blind parallel non-stratified placebo-controlled clinical trial.ParticipantsWe recruited 116 hospitalized patients with severe COVID-19 in Mexico.InterventionsPatients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment.Main measuresThe primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients.Key resultsFifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35-1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66-3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A.ConclusionsColchicine is safe but not effective in the treatment of severe COVID-19.Trial registrationClinicalTrials.gov Identifier: NCT04367168.
| S-EPMC8577644 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1β, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1β and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1β and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment.
| S-EPMC8811745 | biostudies-literature