Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

{ 'indexed': {'date-parts': [[2024, 5, 11]], 'date-time': '2024-05-11T15:14:01Z', 'timestamp': 1715440441054}, 'reference-count': 75, 'publisher': 'Ovid Technologies (Wolters Kluwer Health)', 'issue': '4', 'license': [ { 'start': { 'date-parts': [[2021, 6, 21]], 'date-time': '2021-06-21T00:00:00Z', 'timestamp': 1624233600000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:sec>\n' ' <jats:title>Background:</jats:title>\n' ' <jats:p>Repurposed medicines may have a role against the SARS-CoV-2 virus. The ' 'antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been ' 'tested in numerous clinical trials.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Areas of uncertainty:</jats:title>\n' ' <jats:p>We assessed the efficacy of ivermectin treatment in reducing mortality, ' 'in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, ' 'COVID-19 infection.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Data sources:</jats:title>\n' ' <jats:p>We searched bibliographic databases up to April 25, 2021. Two review ' 'authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were ' 'conducted and certainty of the evidence was assessed using the GRADE approach and ' 'additionally in trial sequential analyses for mortality. Twenty-four randomized controlled ' 'trials involving 3406 participants met review inclusion.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Therapeutic Advances:</jats:title>\n' ' <jats:p>Meta-analysis of 15 trials found that ivermectin reduced risk of death ' 'compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = ' '2438; I<jats:sup>2</jats:sup> = 49%; moderate-certainty evidence). This result was confirmed ' 'in a trial sequential analysis using the same DerSimonian–Laird method that underpinned the ' 'unadjusted analysis. This was also robust against a trial sequential analysis using the ' 'Biggerstaff–Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced ' 'COVID-19 infection by an average 86% (95% confidence interval 79%–91%). Secondary outcomes ' 'provided less certain evidence. Low-certainty evidence suggested that there may be no benefit ' 'with ivermectin for “need for mechanical ventilation,” whereas effect estimates for ' '“improvement” and “deterioration” clearly favored ivermectin use. Severe adverse events were ' 'rare among treatment trials and evidence of no difference was assessed as low certainty. ' 'Evidence on other secondary outcomes was very low certainty.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions:</jats:title>\n' ' <jats:p>Moderate-certainty evidence finds that large reductions in COVID-19 ' 'deaths are possible using ivermectin. Using ivermectin early in the clinical course may ' 'reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ' 'ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic ' 'globally.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1097/mjt.0000000000001402', 'type': 'journal-article', 'created': {'date-parts': [[2021, 6, 19]], 'date-time': '2021-06-19T07:08:05Z', 'timestamp': 1624086485000}, 'page': 'e434-e460', 'source': 'Crossref', 'is-referenced-by-count': 145, 'title': 'Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, ' 'Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines', 'prefix': '10.1097', 'volume': '28', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-4351-8865', 'authenticated-orcid': False, 'given': 'Andrew', 'family': 'Bryant', 'sequence': 'first', 'affiliation': [ { 'name': 'Population Health Sciences Institute, Newcastle University, ' 'Newcastle Upon Tyne, United Kingdom;'}]}, { 'given': 'Theresa A.', 'family': 'Lawrie', 'sequence': 'additional', 'affiliation': [{'name': 'Evidence-based Medicine Consultancy, Bath, United Kingdom;'}]}, { 'given': 'Therese', 'family': 'Dowswell', 'sequence': 'additional', 'affiliation': [{'name': 'Evidence-based Medicine Consultancy, Bath, United Kingdom;'}]}, { 'given': 'Edmund J.', 'family': 'Fordham', 'sequence': 'additional', 'affiliation': [{'name': 'Evidence-based Medicine Consultancy, Bath, United Kingdom;'}]}, { 'given': 'Scott', 'family': 'Mitchell', 'sequence': 'additional', 'affiliation': [ { 'name': 'Emergency Department, Princess Elizabeth Hospital, Guernsey, ' 'United Kingdom; and'}]}, { 'given': 'Sarah R.', 'family': 'Hill', 'sequence': 'additional', 'affiliation': [ { 'name': 'Population Health Sciences Institute, Newcastle University, ' 'Newcastle Upon Tyne, United Kingdom;'}]}, { 'given': 'Tony C.', 'family': 'Tham', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, Ulster Hospital, Dundonald, ' 'Belfast, Northern Ireland, United Kingdom.'}]}], 'member': 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