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

{ 'indexed': { 'date-parts': [[2022, 11, 17]], 'date-time': '2022-11-17T06:12:29Z', 'timestamp': 1668665549830}, 'reference-count': 23, 'publisher': 'Public Library of Science (PLoS)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2022, 11, 16]], 'date-time': '2022-11-16T00:00:00Z', 'timestamp': 1668556800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:sec id="sec001">\n' '<jats:title>Background</jats:title>\n' '<jats:p>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.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods and findings</jats:title>\n' '<jats:p>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.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Conclusion</jats:title>\n' '<jats:p>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.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec004">\n' '<jats:title>Clinical trial registration</jats:title>\n' '<jats:p><jats:bold>Clinical trial registration no:</jats:bold> ClinicalTrials.gov Identifier: ' 'NCT04527562 <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" ' 'xlink:href="https://www.google.com/search?client=firefox-b-d&amp;q=NCT04527562" ' 'xlink:type="simple">https://www.google.com/search?client=firefox-b-d&amp;q=NCT04527562</jats:ext-link>.</jats:p>\n' '</jats:sec>', 'DOI': '10.1371/journal.pone.0277790', 'type': 'journal-article', 'created': { 'date-parts': [[2022, 11, 16]], 'date-time': '2022-11-16T18:34:11Z', 'timestamp': 1668623651000}, 'page': 'e0277790', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, ' 'placebo-controlled trial', 'prefix': '10.1371', 'volume': '17', 'author': [ {'given': 'Motlabur', 'family': 'Rahman', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4508-4549', 'authenticated-orcid': True, 'given': 'Ponkaj K.', 'family': 'Datta', 'sequence': 'additional', 'affiliation': []}, {'given': 'Khairul', 'family': 'Islam', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-2796-2560', 'authenticated-orcid': True, 'given': 'Mahfuzul', 'family': 'Haque', 'sequence': 'additional', 'affiliation': []}, {'given': 'Reaz', 'family': 'Mahmud', 'sequence': 'additional', 'affiliation': []}, {'given': 'Uzzwal', 'family': 'Mallik', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1765-8477', 'authenticated-orcid': True, 'given': 'Pratyay', 'family': 'Hasan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Manjurul', 'family': 'Haque', 'sequence': 'additional', 'affiliation': []}, {'given': 'Imtiaz', 'family': 'Faruq', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohiuddin', 'family': 'Sharif', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rifat H.', 'family': 'Ratul', 'sequence': 'additional', 'affiliation': []}, {'given': 'Khan Abul Kalam', 'family': 'Azad', 'sequence': 'additional', 'affiliation': []}, {'given': 'Titu', 'family': 'Miah', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4381-1511', 'authenticated-orcid': True, 'given': 'Md. 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