High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial
Javier Mariani, Laura Antonietti, Carlos Tajer, León Ferder, Felipe Inserra, Milagro Sanchez Cunto, Diego Brosio, Fernando Ross, Marcelo Zylberman, Daniel Emilio López, Cecilia Luna Hisano, Sebastián Maristany Batisda, Gabriela Pace, Adrián Salvatore, Jimena Fernanda Hogrefe, Marcela Turela, Andrés Gaido, Beatriz Rodera, Elizabeth Banega, María Eugenia Iglesias, Mariela Rzepeski, Juan Manuel Gomez Portillo, Magalí Bertelli, Andrés Vilela, Leandro Heffner, Verónica Laura Annetta, Lucila Moracho, Maximiliano Carmona, Graciela Melito, María José Martínez, Gloria Luna, Natalia Vensentini, Walter Manucha
PLOS ONE, doi:10.1371/journal.pone.0267918
Background The role of oral vitamin D 3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D 3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19.
Methods and findings We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four
Conclusions Supplementation with a single, high dose of vitamin D 3 at admission to patients hospitalized with mild-to-moderate COVID-19 did not prevent respiratory worsening as compared with placebo.
Supporting information S1
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'abstract': '<jats:sec id="sec001">\n'
'<jats:title>Background</jats:title>\n'
'<jats:p>The role of oral vitamin D<jats:sub>3</jats:sub> supplementation for hospitalized '
'patients with COVID-19 remains to be determined. The study was aimed to evaluate whether '
'vitamin D<jats:sub>3</jats:sub> supplementation could prevent respiratory worsening among '
'hospitalized patients with COVID-19.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec002">\n'
'<jats:title>Methods and findings</jats:title>\n'
'<jats:p>We designed a multicentre, randomized, double-blind, sequential, placebo-controlled '
'clinical trial. The study was conducted in 17 second and third level hospitals, located in '
'four provinces of Argentina, from 14 August 2020 to 22 June 2021. We enrolled 218 adult '
'patients, hospitalized in general wards with SARS-CoV-2 confirmed infection, mild-to-moderate '
'COVID-19 and risk factors for disease progression. Participants were randomized to a single '
'oral dose of 500 000 IU of vitamin D<jats:sub>3</jats:sub> or matching placebo. Randomization '
'ratio was 1:1, with permuted blocks and stratified for study site, diabetes and age (≤60 vs '
'>60 years). The primary outcome was the change in the respiratory Sepsis related Organ '
'Failure Assessment score between baseline and the highest value recorded up to day 7. '
'Secondary outcomes included the length of hospital stay; intensive care unit admission; and '
'in-hospital mortality. Overall, 115 participants were assigned to vitamin '
'D<jats:sub>3</jats:sub> and 105 to placebo (mean [SD] age, 59.1 [10.7] years; 103 [47.2%] '
'women). There were no significant differences in the primary outcome between groups (median '
'[IQR] 0.0 [0.0–1.0] vs 0.0 [0.0–1.0], for vitamin D<jats:sub>3</jats:sub> and placebo, '
'respectively; <jats:italic>p</jats:italic> = 0.925). Median [IQR] length of hospital stay was '
'not significantly different between vitamin D<jats:sub>3</jats:sub> group (6.0 [4.0–9.0] '
'days) and placebo group (6.0 [4.0–10.0] days; <jats:italic>p</jats:italic> = 0.632). There '
'were no significant differences for intensive care unit admissions (7.8% vs 10.7%; RR 0.73; '
'95% CI 0.32 to 1.70; <jats:italic>p</jats:italic> = 0.622), or in-hospital mortality (4.3% vs '
'1.9%; RR 2.24; 95% CI 0.44 to 11.29; <jats:italic>p</jats:italic> = 0.451). There were no '
'significant differences in serious adverse events (vitamin D<jats:sub>3</jats:sub> = 14.8%, '
'placebo = 11.7%).</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec003">\n'
'<jats:title>Conclusions</jats:title>\n'
'<jats:p>Among hospitalized patients with mild-to-moderate COVID-19 and risk factors, a single '
'high oral dose of vitamin D<jats:sub>3</jats:sub> as compared with placebo, did not prevent '
'the respiratory worsening.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec004">\n'
'<jats:title>Trial registration</jats:title>\n'
'<jats:p>ClincicalTrials.gov Identifier: <jats:ext-link '
'xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" '
'xlink:href="https://clinicaltrials.gov/show/NCT04411446" '
'xlink:type="simple">NCT04411446</jats:ext-link>.</jats:p>\n'
'</jats:sec>',
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