Dataset Information

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.

ABSTRACT:

Background

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.

Methods

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 (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed.

Results

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. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 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. 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 (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes.

Conclusions

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.

Trial registration

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 ( NCT04552951 ).

SUBMITTER: Cannata-Andia JB

PROVIDER: S-EPMC8853840 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint was the area under the curve (AUC) of serum 25-hydroxyvitamin-D (25(OH)D) concentrations on Day 112. This study was conducted in France from February to June 2014 in 53 young adults with a mean age of 26.9 years. At baseline, low mean serum 25(OH)D levels were observed in both groups (10.6 ng/mL in Group 1 and 9.0 ng/mL in Group 2). On Day 112, the AUC of serum 25(OH)D concentration was 2499.4 ± 463.8 nmol/mL (7.8 ± 0.2 for LogAUC) for Group 1 and 2152.3 ± 479.8 nmol/mL (7.6 ± 0.2 for LogAUC) for Group 2. Bioequivalence of the two treatments was not demonstrated. Superiority of vitamin D3 100,000 IU soft capsule was observed with p = 0.029 for AUC and p = 0.03 for LogAUC using a non-parametric Wilcoxon test. The profile of the serum 25(OH)D concentration showed a significant difference in favor of Group 1 on Days 1, 3, 7, 14 and 90. Mean serum 25(OH)D concentrations in Group 1 were between 20 and 30 ng/mL during the four-month period and under 20 ng/mL throughout the study in Group 2, except on Day 112. Mean Cmax for Group 1 was significantly higher (p = 0.002). Fourteen days were needed to reach Tmax by more than half the subjects in Group 1 compared to 45 days in Group 2. Both treatments were well tolerated, with no severe or related adverse events reported. In conclusion, the pharmacokinetic profile of the new formulation of vitamin D3 100,000 IU soft capsule is superior to that of the oral solution in ampoule. The new formulation increased serum 25(OH)D levels to above 20 ng/mL and maintained levels from 20 ng/mL to 30 ng/mL for four months in late winter and spring.

Project description:BackgroundNew evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D3 in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes.MethodsWe conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1-5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D3 (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (Δ25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD ≥ 75 nmol/L, safety, and adverse event rates.ResultsChildren (N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the Δ25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time (p < 0.0001) and group*time interaction effect (p < 0.0001), in favour of the intervention. A significant group difference in the Δ25OHD was observed 10 days after the first (119.3 [105.8, 132.9] nmol/L) and second (100.1 [85.7, 114.6] nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (≥ 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child.ConclusionTwo oral boluses of 100,000 IU vitamin D3,once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD ≥ 75 nmol/L throughout 7 months in only slightly more than half of participants.Trial registrationClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014.