ABSTRACT
BACKGROUND: The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D3 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 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 D3 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 D3 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 D3 and placebo, respectively; p = 0.925). Median [IQR] length of hospital stay was not significantly different between vitamin D3 group (6.0 [4.0-9.0] days) and placebo group (6.0 [4.0-10.0] days; p = 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; p = 0.622), or in-hospital mortality (4.3% vs 1.9%; RR 2.24; 95% CI 0.44 to 11.29; p = 0.451). There were no significant differences in serious adverse events (vitamin D3 = 14.8%, placebo = 11.7%). CONCLUSIONS: Among hospitalized patients with mild-to-moderate COVID-19 and risk factors, a single high oral dose of vitamin D3 as compared with placebo, did not prevent the respiratory worsening. TRIAL REGISTRATION: ClincicalTrials.gov Identifier: NCT04411446.
Subject(s)
COVID-19 Drug Treatment , Vitamin D , Adult , Cholecalciferol , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Vitamin D/therapeutic use , Vitamins/therapeutic useABSTRACT
BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).