Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients

{ 'indexed': {'date-parts': [[2024, 4, 8]], 'date-time': '2024-04-08T20:30:56Z', 'timestamp': 1712608256183}, 'reference-count': 30, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2021, 5, 4]], 'date-time': '2021-05-04T00:00:00Z', 'timestamp': 1620086400000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}, { 'start': { 'date-parts': [[2021, 5, 4]], 'date-time': '2021-05-04T00:00:00Z', 'timestamp': 1620086400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2021, 12]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Background and objectives</jats:title>\n' ' <jats:p>An effective treatment option is not yet available for SARS-CoV2, ' 'which causes the COVID-19 pandemic and whose effects are felt more and more every day. ' 'Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this ' 'study; it was aimed to investigate the presence of gene mutations that alter ivermectin ' 'metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to ' 'evaluate the effectiveness and safety of ivermectin use in the treatment of patients without ' 'mutation.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Materials and methods</jats:title>\n' ' <jats:p>Patients with severe COVID19 pneumonia were included in the study, ' 'which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two ' 'groups, the study group and the control group, took part in the study. Ivermectin 200 ' 'mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the ' 'reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients ' 'included in the study group. Patients in the control group were given only reference ' 'treatment with 3 other drugs without ivermectin. The presence of mutations was investigated ' 'by performing sequence analysis in the <jats:italic>mdr1/abcab1</jats:italic> gene with the ' 'Sanger method in patients included in the study group according to randomization. Patients ' 'with mutations were excluded from the study and ivermectin treatment was not continued. ' 'Patients were followed for 5\u2009days after treatment. At the end of the treatment and ' 'follow-up period, clinical response and changes in laboratory parameters were ' 'evaluated.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>A total of 66 patients, 36 in the study group and 30 in the control ' 'group were included in the study. Mutations affecting ivermectin metabolism was detected in ' 'genetic tests of six (16.7%) patients in the study group and they were excluded from the ' 'study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% ' '(22/30) in the study group and was 53.3% (16/30) in the control group (<jats:italic>p\u2009' '=\u20090.10</jats:italic>). At the end of the study, mortality developed in 6 patients (20%) ' 'in the study group and in 9 (30%) patients in the control group (<jats:italic>p\u2009=\u2009' '0.37</jats:italic>). At the end of the follow-up period, the average peripheral capillary ' 'oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and ' '93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as ' '236.3\u2009±\u200985.7 and 220.8\u2009±\u2009127.3 in the study and control groups, ' 'respectively. While the blood lymphocyte count was higher in the study group compared to the ' 'control group (1698\u2009±\u20091438 and 1256\u2009±\u2009710, respectively) at the end of ' 'the follow-up period (<jats:italic>p\u2009=\u20090.24</jats:italic>); reduction in serum ' 'C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group ' '(<jats:italic>p\u2009=\u20090.02, p\u2009=\u20090.005 and p\u2009=\u20090.03</jats:italic>, ' 'respectively).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>According to the findings obtained, ivermectin can provide an ' 'increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease ' 'in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin ' 'should be considered as an alternative drug that can be used in the treatment of COVID-19 ' 'disease or as an additional option to existing protocols.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s12879-021-06104-9', 'type': 'journal-article', 'created': {'date-parts': [[2021, 5, 4]], 'date-time': '2021-05-04T08:04:55Z', 'timestamp': 1620115495000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 63, 'title': 'Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 ' 'patients', 'prefix': '10.1186', 'volume': '21', 'author': [ {'given': 'Nurullah', 'family': 'Okumuş', 'sequence': 'first', 'affiliation': []}, {'given': 'Neşe', 'family': 'Demirtürk', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rıza Aytaç', 'family': 'Çetinkaya', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rahmet', 'family': 'Güner', 'sequence': 'additional', 'affiliation': []}, {'given': 'İsmail Yaşar', 'family': 'Avcı', 'sequence': 'additional', 'affiliation': []}, {'given': 'Semiha', 'family': 'Orhan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Petek', 'family': 'Konya', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bengü', 'family': 'Şaylan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ayşegül', 'family': 'Karalezli', 'sequence': 'additional', 'affiliation': []}, {'given': 'Levent', 'family': 'Yamanel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bircan', 'family': 'Kayaaslan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gülden', 'family': 'Yılmaz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ümit', 'family': 'Savaşçı', 'sequence': 'additional', 'affiliation': []}, {'given': 'Fatma', 'family': 'Eser', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gürhan', 'family': 'Taşkın', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2021, 5, 4]]}, 'reference': [ { 'issue': '18', 'key': '6104_CR1', 'doi-asserted-by': 'publisher', 'first-page': '1708', 'DOI': '10.1056/NEJMoa2002032', 'volume': '382', 'author': 'WJ Guan', 'year': '2020', 'unstructured': 'Guan WJ, Ni ZY, Hu Y, et al. 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