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All Studies   Meta Analysis    Recent:   

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial

Annweiler et al., PLoS Medicine, doi:10.1371/journal.pmed.1003999, COVIT-TRIAL, NCT04344041
May 2022  
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Mortality, ITT, day 28 30% Improvement Relative Risk Mortality, PP, day 28 38% Mortality, ITT, day 14 61% Mortality, PP, day 14 65% Vitamin D  COVIT-TRIAL  EARLY TREATMENT  RCT Is early treatment with vitamin D beneficial for COVID-19? RCT 254 patients in France (April - December 2020) Lower mortality with vitamin D (not stat. sig., p=0.29) c19early.org Annweiler et al., PLoS Medicine, May 2022 Favorshigh dose Favorslow dose 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 121 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19early.org
RCT comparing single dose 400,000IU and single dose 50,000IU vitamin D in France, showing lower mortality with the higher dose, statistically significant only at day 14.
The aHR for days 0-5 was 1.30 [0.31-5.35], compared to 0.11 [0.02-0.52] for days 6-14, which in part may reflect the conversion delay for cholecalciferol treatment. The lower efficacy at day 28 vs. day 14 may in part reflect use of only a single dose.
Bolus treatment is less effective. Pharmacokinetics and the potential side effects of high bolus doses suggest that ongoing treatment spread over time is more appropriate. Research has confirmed that lower dose regular treatment with vitamin D is more effective than intermittent high-dose bolus treatment for various conditions, including rickets and acute respiratory infections1,2. The biological mechanisms supporting these findings involve the induction of enzymes such as 24-hydroxylase and fibroblast growth factor 23 (FGF23) by high-dose bolus treatments. These enzymes play roles in inactivating vitamin D, which can paradoxically reduce levels of activated vitamin D and suppress its activation for extended periods post-dosage. Evidence indicates that 24-hydroxylase activity may remain elevated for several weeks following a bolus dose, leading to reduced levels of the activated form of vitamin D. Additionally, FGF23 levels can increase for at least three months after a large bolus dose, which also contributes to the suppression of vitamin D activation1.
risk of death, 30.0% lower, HR 0.70, p = 0.29, treatment 19 of 126 (15.1%), control 21 of 126 (16.7%), Cox proportional hazards, day 28, intention-to-treat.
risk of death, 38.0% lower, HR 0.62, p = 0.17, treatment 17 of 121 (14.0%), control 21 of 121 (17.4%), Cox proportional hazards, day 28, per-protocol.
risk of death, 61.0% lower, HR 0.39, p = 0.049, treatment 8 of 127 (6.3%), control 14 of 127 (11.0%), Cox proportional hazards, day 14, intention-to-treat.
risk of death, 65.0% lower, HR 0.35, p = 0.03, treatment 7 of 122 (5.7%), control 14 of 122 (11.5%), Cox proportional hazards, day 14, per-protocol.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Annweiler et al., 31 May 2022, Randomized Controlled Trial, France, peer-reviewed, 17 authors, study period 15 April, 2020 - 17 December, 2020, dosage 400,000IU single dose, trial NCT04344041 (history) (COVIT-TRIAL).
This PaperVitamin DAll
High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial
Cédric Annweiler, Mélinda Beaudenon, Jennifer Gautier, Justine Gonsard, Sophie Boucher, Guillaume Chapelet, Astrid Darsonval, Bertrand Fougère, Olivier Guérin, Marjorie Houvet, Pierre Ménager, Claire Roubaud-Baudron, Achille Tchalla, Jean-Claude Souberbielle, Jérémie Riou, Elsa Parot-Schinkel, Thomas Célarier
PLOS Medicine, doi:10.1371/journal.pmed.1003999
¶ Membership of the COVIT-TRIAL study group is provided in S1 Supplemental Appendix.
Supporting information S1
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