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REsCue Trial: Randomized Controlled Clinical Trial with Extended-Release Calcifediol in Symptomatic COVID-19 Outpatients

Bishop et al., Nutrition, doi:10.1016/j.nut.2022.111899 (date from preprint), REsCue, NCT04551911
Feb 2022  
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ER/urgent care visits 85% Improvement Relative Risk Recovery 34% Recovery (b) 73% Recovery (c) 58% Recovery (d) -6% Recovery (e) -3% Resolution of 5 aggregate.. 9% Vitamin D  REsCue  LATE TREATMENT  DB RCT Is late treatment with vitamin D beneficial for COVID-19? Double-blind RCT 134 patients in the USA (November 2020 - October 2021) Lower progression (p=0.25) and improved recovery (p=0.56), not sig. Bishop et al., Nutrition, February 2022 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. * >10% efficacy, ≥3 studies.
4,300+ studies for 77 treatments.
Small RCT with low-risk patients in the USA showing no significant differences in overall recovery. Minimal details on outcomes are provided in the preprint. Authors note significantly faster resolution of respiratory symptoms when treatment increased vitamin D levels. Baseline vitamin D was relatively high, mean 37±1 ng/mL, 95% >20ng/mL, leaving little room for improvement. Treatment delay is not specified but is likely relatively late based on the symptoms at baseline, PCR testing delay, and exclusion with FLU-PRO scores <1.5. ER/urgent care data from
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 10th of 30 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000032.
This is the 69th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
ER/urgent care visits, 85.4% lower, RR 0.15, p = 0.25, treatment 0 of 65 (0.0%), control 3 of 69 (4.3%), NNT 23, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of no recovery, 33.7% lower, RR 0.66, p = 0.56, treatment 5 of 65 (7.7%), control 8 of 69 (11.6%), NNT 26, day 21, mid-trial.
risk of no recovery, 73.5% lower, RR 0.27, p = 0.37, treatment 1 of 65 (1.5%), control 4 of 69 (5.8%), NNT 23, day 35.
risk of no recovery, 57.5% lower, RR 0.42, p = 0.44, treatment 2 of 65 (3.1%), control 5 of 69 (7.2%), NNT 24, day 28.
risk of no recovery, 6.2% higher, RR 1.06, p = 0.85, treatment 17 of 65 (26.2%), control 17 of 69 (24.6%), day 14.
risk of no recovery, 3.0% higher, RR 1.03, p = 1.00, treatment 33 of 65 (50.8%), control 34 of 69 (49.3%), day 7.
resolution of 5 aggregated symptoms, 9.3% lower, relative time 0.91, p = 0.52, treatment mean 9.8 (±8.15) n=65, control mean 10.8 (±9.54) n=69.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bishop et al., 5 Feb 2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, survey, 11 authors, study period 2 November, 2020 - 8 October, 2021, dosage calcifediol 300μg days 1-3, 60μg days 4-27, trial NCT04551911 (history) (REsCue). Contact:
This PaperVitamin DAll
REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients
Charles W Bishop, Akhtar Ashfaq, Joel Z Melnick, Enrique Vazquez-Escarpanter, Jonathan A Fialkow, PhD Stephen A Strugnell, John Choe, Kamyar Kalantar-Zadeh, Noah C Federman, David Ng, John S Adams
Nutrition, doi:10.1016/j.nut.2022.111899
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
CONCLUSIONS In conclusion, ERC was effective in increasing serum total 25D to levels of at least 50 ng/mL in outpatients with mild to moderate COVID-19 and may have accelerated resolution of respiratory symptoms, suggesting mitigation of COVID-19 pneumonia risk. The positive findings from this RCT warrant confirmation in additional larger studies. Data Availability: Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.
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Late treatment
is less effective
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