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Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment...

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Autores principales: Rahman, Motlabur, Datta, Ponkaj K., Islam, Khairul, Haque, Mahfuzul, Mahmud, Reaz, Mallik, Uzzwal, Hasan, Pratyay, Haque, Manjurul, Faruq, Imtiaz, Sharif, Mohiuddin, Ratul, Rifat H., Azad, Khan Abul Kalam, Miah, Titu, Rahman, Md. Mujibur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668149/
https://www.ncbi.nlm.nih.gov/pubmed/36383611
http://dx.doi.org/10.1371/journal.pone.0277790
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author Rahman, Motlabur
Datta, Ponkaj K.
Islam, Khairul
Haque, Mahfuzul
Mahmud, Reaz
Mallik, Uzzwal
Hasan, Pratyay
Haque, Manjurul
Faruq, Imtiaz
Sharif, Mohiuddin
Ratul, Rifat H.
Azad, Khan Abul Kalam
Miah, Titu
Rahman, Md. Mujibur
author_facet Rahman, Motlabur
Datta, Ponkaj K.
Islam, Khairul
Haque, Mahfuzul
Mahmud, Reaz
Mallik, Uzzwal
Hasan, Pratyay
Haque, Manjurul
Faruq, Imtiaz
Sharif, Mohiuddin
Ratul, Rifat H.
Azad, Khan Abul Kalam
Miah, Titu
Rahman, Md. Mujibur
author_sort Rahman, Motlabur
collection PubMed
description BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many anti-inflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1β) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality. METHODS AND FINDINGS: This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes were also recorded on day 28. The primary endpoint was met by 9 (6.2%) patients in the placebo group and 4 (2.7%) patients in the colchicine group (P = 0.171), which corresponds to a hazard ratio (95% CI) of 0.44 (0.13–1.43). Additional analysis of the outcomes on day 28 revealed significantly lower clinical deterioration (defined as a decrease by two or more points) in the colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098–0.917], (P = 0.035). Despite a 56% reduction in the need for mechanical ventilation and death with colchicine treatment on day 14, the reduction was not statistically significant. On day 28, colchicine significantly reduced clinical deterioration measured as the need for mechanical ventilation and all-cause mortality. CONCLUSION: Colchicine was not found to have a significant beneficial effect on reducing mortality and the need for mechanical ventilation. However, a delayed beneficial effect was observed. Therefore, further studies should be conducted to evaluate the late benefits of colchicine. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: ClinicalTrials.gov Identifier: NCT04527562 https://www.google.com/search?client=firefox-b-d&q=NCT04527562.
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spelling pubmed-96681492022-11-17 Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial Rahman, Motlabur Datta, Ponkaj K. Islam, Khairul Haque, Mahfuzul Mahmud, Reaz Mallik, Uzzwal Hasan, Pratyay Haque, Manjurul Faruq, Imtiaz Sharif, Mohiuddin Ratul, Rifat H. Azad, Khan Abul Kalam Miah, Titu Rahman, Md. Mujibur PLoS One Research Article BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many anti-inflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1β) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality. METHODS AND FINDINGS: This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes were also recorded on day 28. The primary endpoint was met by 9 (6.2%) patients in the placebo group and 4 (2.7%) patients in the colchicine group (P = 0.171), which corresponds to a hazard ratio (95% CI) of 0.44 (0.13–1.43). Additional analysis of the outcomes on day 28 revealed significantly lower clinical deterioration (defined as a decrease by two or more points) in the colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098–0.917], (P = 0.035). Despite a 56% reduction in the need for mechanical ventilation and death with colchicine treatment on day 14, the reduction was not statistically significant. On day 28, colchicine significantly reduced clinical deterioration measured as the need for mechanical ventilation and all-cause mortality. CONCLUSION: Colchicine was not found to have a significant beneficial effect on reducing mortality and the need for mechanical ventilation. However, a delayed beneficial effect was observed. Therefore, further studies should be conducted to evaluate the late benefits of colchicine. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: ClinicalTrials.gov Identifier: NCT04527562 https://www.google.com/search?client=firefox-b-d&q=NCT04527562. Public Library of Science 2022-11-16 /pmc/articles/PMC9668149/ /pubmed/36383611 http://dx.doi.org/10.1371/journal.pone.0277790 Text en © 2022 Rahman et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rahman, Motlabur
Datta, Ponkaj K.
Islam, Khairul
Haque, Mahfuzul
Mahmud, Reaz
Mallik, Uzzwal
Hasan, Pratyay
Haque, Manjurul
Faruq, Imtiaz
Sharif, Mohiuddin
Ratul, Rifat H.
Azad, Khan Abul Kalam
Miah, Titu
Rahman, Md. Mujibur
Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title_full Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title_fullStr Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title_full_unstemmed Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title_short Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
title_sort efficacy of colchicine in patients with moderate covid-19: a double-blinded, randomized, placebo-controlled trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668149/
https://www.ncbi.nlm.nih.gov/pubmed/36383611
http://dx.doi.org/10.1371/journal.pone.0277790
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