A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D — a randomised multicentre international clinical trial

DOI record: { "DOI": "10.1186/s12916-022-02290-8", "ISSN": [ "1741-7015" ], "URL": "http://dx.doi.org/10.1186/s12916-022-02290-8", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (<jats:italic>n</jats:italic>=274) or nothing (<jats:italic>n</jats:italic>=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs<jats:italic>.</jats:italic> 16.1 ng/mL at admission and 29.0 vs<jats:italic>.</jats:italic> 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0–10.5] vs<jats:italic>.</jats:italic> 9.5 [95%CI 9.0–10.5] days), admission to ICU (17.2% [95%CI 13.0–22.3] vs. 16.4% [95%CI 12.3–21.4]) and death rate (8.0% [95%CI 5.2–12.1] vs<jats:italic>.</jats:italic> 5.6% [95%CI 3.3–9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (&gt;25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Trial registration</jats:title>\n <jats:p>COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/ct2/show/NCT04552951\">NCT04552951</jats:ext-link>).</jats:p>\n </jats:sec>", "alternative-id": [ "2290" ], "article-number": "83", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "30 August 2021" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "9 February 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "18 February 2022" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The ethics committees of all participating centre approved the study. Due to the COVID-19 pandemic and in order to avoid unnecessary exposure to the SARS-CoV-2 virus, all ethics committees authorized verbal consent. The trial was conducted according to the ethical principles of the Declaration of Helsinki." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The following authors received research grants fees, grants for congress attending, courses and collaborations by the following entities: Jorge B. Cannata-Andía from Amgen, Kyowa-Kirim and Vifor Pharma; Ricardo Mouzo from Takeda, Otsuka, Nipro, Sanofi-Aventis, Amgen and the Senefro Foundation; Natalia Carrillo-López from Ministerio de Ciencia e Innovación (MICINN)/Instituto de Salud Carlos III (ISCIII); Sara Panizo from MICINN/ISCIII and Luis Hernando gran from Fundación Renal Íñigo Álvarez de Toledo; Carolina Ballarino from Pfizer, Takeda and Sanofi-Aventis; Jacqueline Pefaur-Penna from Novartis and Sanofi-Aventis; Jesús Calviño-Varela from Baxter, Otsuka, Palex, Astra, Vifor and Chiesi; Carlos Gómez-Alonso from Amgen, UCB, Stada, Grünenthal, Gebro Pharma, FAES, Kiowa-Kirin and Laboratorios Rubió; John Cunningham from Amgen, Merck and Vifor Pharma; Manuel Naves-Díaz from MICINN/ISCIII, Amgen, UCB, Kyowa-Kirim, Stada, Italfármaco, Gebro Pharma, Rubió, Gedeon Richter, Grünenthal and FEIOMM and José L. Fernández-Martín from MICINN/ISCIII. The rest of authors are not aware of any additional relationship, funding or financial holdings." } ], "author": [ { "ORCID": "http://orcid.org/0000-0001-6543-9960", "affiliation": [], "authenticated-orcid": false, "family": "Cannata-Andía", "given": "Jorge B.", "sequence": "first" }, { "affiliation": [], "family": "Díaz-Sottolano", "given": "Augusto", "sequence": "additional" }, { "affiliation": [], "family": "Fernández", "given": "Pehuén", "sequence": "additional" }, { "affiliation": [], "family": "Palomo-Antequera", "given": "Carmen", "sequence": "additional" }, { "affiliation": [], "family": "Herrero-Puente", "given": "Pablo", "sequence": "additional" }, { "affiliation": [], "family": "Mouzo", "given": "Ricardo", "sequence": "additional" }, { "affiliation": [], "family": "Carrillo-López", "given": "Natalia", "sequence": "additional" }, { "affiliation": [], "family": "Panizo", "given": "Sara", "sequence": "additional" }, { "affiliation": [], "family": "Ibañez", "given": "Guillermo H.", "sequence": "additional" }, { "affiliation": [], "family": "Cusumano", "given": "Carlos A.", "sequence": "additional" }, { "affiliation": [], "family": "Ballarino", "given": "Carolina", "sequence": "additional" }, { "affiliation": [], "family": "Sánchez-Polo", "given": "Vicente", "sequence": "additional" }, { "affiliation": [], "family": "Pefaur-Penna", "given": "Jacqueline", "sequence": "additional" }, { "affiliation": [], "family": "Maderuelo-Riesco", "given": "Irene", "sequence": "additional" }, { "affiliation": [], "family": "Calviño-Varela", "given": "Jesús", "sequence": "additional" }, { "affiliation": [], "family": "Gómez", "given": "Mónica D.", "sequence": "additional" }, { "affiliation": [], "family": "Gómez-Alonso", "given": "Carlos", "sequence": "additional" }, { "affiliation": [], "family": "Cunningham", "given": "John", "sequence": "additional" }, { "affiliation": [], "family": "Naves-Díaz", "given": "Manuel", "sequence": "additional" }, { "affiliation": [], "family": "Douthat", "given": "Walter", "sequence": "additional" }, { "affiliation": [], "family": "Fernández-Martín", "given": "José L.", "sequence": "additional" }, { "affiliation": [], "name": "the COVID-VIT-D trial collaborators", "sequence": "additional" } ], "container-title": [ "BMC Medicine" ], "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2022, 2, 18 ] ], "date-time": "2022-02-18T02:02:49Z", "timestamp": 1645149769000 }, "deposited": { "date-parts": [ [ 2022, 2, 19 ] ], "date-time": "2022-02-19T00:25:22Z", "timestamp": 1645230322000 }, "indexed": { "date-parts": [ [ 2022, 2, 19 ] ], "date-time": "2022-02-19T00:40:40Z", "timestamp": 1645231240449 }, "is-referenced-by-count": 0, "issn-type": [ { "type": "electronic", "value": "1741-7015" } ], "issue": "1", "issued": { "date-parts": [ [ 2022, 2, 18 ] ] }, "journal-issue": { "issue": "1", "published-print": { "date-parts": [ [ 2022, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 2, 18 ] ], "date-time": "2022-02-18T00:00:00Z", "timestamp": 1645142400000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 2, 18 ] ], "date-time": "2022-02-18T00:00:00Z", "timestamp": 1645142400000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12916-022-02290-8.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12916-022-02290-8/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12916-022-02290-8.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2022, 2, 18 ] ] }, "published-online": { "date-parts": [ [ 2022, 2, 18 ] ] }, "published-print": { "date-parts": [ [ 2022, 12 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1007/978-1-60327-303-9", "author": "MF Holick", "doi-asserted-by": "crossref", "key": "2290_CR1", "unstructured": "Holick MF, Vitamin D. 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