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Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study

Entrenas Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751, COVIDIOL, NCT04366908
Aug 2020  
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Mortality 85% Improvement Relative Risk ICU admission 94% Vitamin D  COVIDIOL  LATE TREATMENT  RCT Is late treatment with vitamin D beneficial for COVID-19? RCT 76 patients in Spain (May - June 2020) Lower ICU admission with vitamin D (p=0.008) c19early.org Entrenas Castillo et al., J. Steroid B.., Aug 2020 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. For additional analysis see Jungreis et al.1.
Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 69% [47‑82%] lower risk vs. 39% [27‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.
This is the 1st of 30 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000032.
This is the 3rd of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
risk of death, 85.4% lower, RR 0.15, p = 0.11, treatment 0 of 50 (0.0%), control 2 of 26 (7.7%), NNT 13, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 94.2% lower, RR 0.06, p = 0.008, treatment 1 of 50 (2.0%), control 13 of 26 (50.0%), NNT 2.1, odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Entrenas Castillo et al., 29 Aug 2020, Randomized Controlled Trial, Spain, peer-reviewed, 7 authors, study period May 2020 - June 2020, dosage calcifediol 0.5mg day 1, 0.27mg day 3, 0.27mg day 7, and then weekly until discharge or ICU admission, trial NCT04366908 (history) (COVIDIOL).
This PaperVitamin DAll
Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study
Marta Entrenas-Castillo, Luis Manuel Entrenas-Costa, María P Pata, Bernabe Jurado-Gamez, Cristina Muñoz-Corroto, Cristina Gomez-Rebollo, Estefania Mira-Padilla, Roger Bouillon, Jose Manuel Quesada-Gómez
Nutrients, doi:10.3390/nu16121910
Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. Objective: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. Design, patients and setting: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). Interventions: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. Measurements: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. Results: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. Interpretation: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.
Funding: This study was funded by an Intramural Grant of Clinical trial funds (ECL 026) from FIBICO (Fundación del Instituto Maimónides de Investigación Biomédica de Córdoba). Institutional Review Board Statement: The study was approved by the Biomedical Research Ethics Committee of the Hospital Universitario Reina Sofía de Córdoba (committee reference number 5291) Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. The funder (FIBICO) had no role in the design of the study; in the collection, analyses or interpretation of the data; in the writing of the manuscript or in the decision to publish the results.
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Late treatment
is less effective
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