Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype

{ 'indexed': { 'date-parts': [[2022, 11, 30]], 'date-time': '2022-11-30T09:29:30Z', 'timestamp': 1669800570802}, 'reference-count': 83, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2022, 7, 23]], 'date-time': '2022-07-23T00:00:00Z', 'timestamp': 1658534400000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2022, 7, 23]], 'date-time': '2022-07-23T00:00:00Z', 'timestamp': 1658534400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100004901', 'name': 'Fundação de Amparo à Pesquisa do Estado de Minas Gerais', 'doi-asserted-by': 'publisher', 'award': ['APQ-01154-21']}, { 'DOI': '10.13039/501100003593', 'name': 'Conselho Nacional de Desenvolvimento Científico e Tecnológico', 'doi-asserted-by': 'publisher', 'award': ['310561/2021-3', '465518/2014-1']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2022, 12]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>The role of ivermectin in the treatment of COVID-19 is still under ' 'debate, yet the drug has been widely used in some parts of the world, as shown by impressive ' 'market data. The available body of evidence may have changed over the last months, as studies ' 'have been retracted and “standards of care” (SOC) used in control groups have changed with ' 'rapidly evolving knowledge on COVID-19. This review aims to summarize and critically appraise ' 'the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical ' 'outcomes in COVID-19 patients.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>RCTs evaluating the effects of ivermectin in adult patients with ' 'COVID-19 were searched through June 22, 2022, in four databases, L.OVE platform, clinical ' 'trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and ' 'invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. ' 'Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Meta-analysis included ' 'only studies which compared ivermectin to placebo or SOC. Random-effects were used to pool ' 'the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using ' 'GRADE. The protocol was register in PROSPERO (CRD42021257471).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Twenty-five RCTs fulfilled inclusion criteria (n\u2009=\u20096310). ' 'Of those, 14 compared ivermectin with placebo, in night ivermectin associated with SOC was ' 'compared to SOC and two studies compared ivermectin to an active comparator. Most RCTs had ' 'some concerns or high risk of bias, mostly due to lack of concealment of the randomization ' 'sequence and allocation, lack of blinding and high number of missing cases. Ivermectin did ' 'not show an effect in reducing mortality (RR\u2009=\u20090.76; 95%CI: 0.52–1.11) or ' 'mechanical ventilation (RR\u2009=\u20090.74; 95%CI: 0.48–1.16). This effect was consistent ' 'when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as ' 'in sensitivity analysis. Additionally, there was very low quality of evidence regarding ' 'adverse effects (RR\u2009=\u20091.07; 95%CI: 0.84–1.35).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>The evidence suggests that ivermectin does not reduce mortality risk ' 'and the risk of mechanical ventilation requirement. Although we did not observe an increase ' 'in the risk of adverse effects, the evidence is very uncertain regarding this ' 'endpoint.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s12879-022-07589-8', 'type': 'journal-article', 'created': {'date-parts': [[2022, 7, 23]], 'date-time': '2022-07-23T10:03:17Z', 'timestamp': 1658570597000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 4, 'title': 'Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the ' 'hype', 'prefix': '10.1186', 'volume': '22', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-4278-3771', 'authenticated-orcid': False, 'given': 'Milena Soriano', 'family': 'Marcolino', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1722-5703', 'authenticated-orcid': False, 'given': 'Karina Cardoso', 'family': 'Meira', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0487-0500', 'authenticated-orcid': False, 'given': 'Nathalia Sernizon', 'family': 'Guimarães', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5757-7255', 'authenticated-orcid': False, 'given': 'Paula Perdigão', 'family': 'Motta', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9058-2803', 'authenticated-orcid': False, 'given': 'Victor Schulthais', 'family': 'Chagas', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Silvana Márcia Bruschi', 'family': 'Kelles', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0845-5814', 'authenticated-orcid': False, 'given': 'Laura Caetano', 'family': 'de Sá', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-2666-7092', 'authenticated-orcid': False, 'given': 'Reginaldo Aparecido', 'family': 'Valacio', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-2851-2011', 'authenticated-orcid': False, 'given': 'Patrícia Klarmann', 'family': 'Ziegelmann', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2022, 7, 23]]}, 'reference': [ { 'key': '7589_CR1', 'doi-asserted-by': 'publisher', 'author': 'T Burki', 'year': '2020', 'unstructured': 'Burki T. 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