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REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.
Bishop, CW, Ashfaq, A, Melnick, JZ, Vazquez-Escarpanter, E, Fialkow, JA, Strugnell, SA, Choe, J, Kalantar-Zadeh, K, Federman, NC, Ng, D, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2023;107:111899
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Literature shows that vitamin D repletion may reduce the risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigate severity of coronavirus disease (COVID-19), and accelerate recovery. Sufficient serum level of 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness, boost innate and control adaptive immunity, and reduce post-infection cytokine storm and lung injury. The aim of this study was to evaluate the safety and efficacy of extended-release calcifediol capsules to treat symptomatic patients infected with SARS-CoV-2. This study is a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial titled REsCue. One hundred seventy-one symptomatic COVID-19 outpatients participants were enrolled. Patients were randomised (1:1) to 4 weeks of treatment with extended-release calcifediol (30 mcg/capsule) or matching placebo and a 2-week follow-up. Results show that extended-release calcifediol treatment was effective in increasing serum 25D levels to ≥50 ng/mL, which may have yielded significantly shorter resolution times for three aggregated respiratory symptoms (trouble breathing, chest congestion, and dry or hacking cough) commonly observed in patients with mild to moderate COVID-19. Authors conclude that the positive findings from this study warrant confirmation in additional larger studies.
Abstract
OBJECTIVES This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.
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Model for assessing cardiovascular risk in a Korean population.
Park, GM, Han, S, Kim, SH, Jo, MW, Her, SH, Lee, JB, Lee, MS, Kim, HC, Ahn, JM, Lee, SW, et al
Circulation. Cardiovascular quality and outcomes. 2014;(6):944-51
Abstract
BACKGROUND A model for predicting cardiovascular disease in Asian populations is limited. METHODS AND RESULTS In total, 57 393 consecutive asymptomatic Korean individuals aged 30 to 80 years without a prior history of cardiovascular disease who underwent a general health examination were enrolled. Subjects were randomly classified into the train (n=45 914) and validation (n=11 479) cohorts. Thirty-one possible risk factors were assessed. The cardiovascular event was a composite of cardiovascular death, myocardial infarction, and stroke. In the train cohort, the C-index (95% confidence interval) and Akaike Information Criterion were used to develop the best-fitting prediction model. In the validation cohort, the predicted versus the observed cardiovascular event rates were compared by the C-index and Nam and D'Agostino χ(2) statistics. During a median follow-up period of 3.1 (interquartile range, 1.9-4.3) years, 458 subjects had 474 cardiovascular events. In the train cohort, the best-fitting model consisted of age, diabetes mellitus, hypertension, current smoking, family history of coronary heart disease, white blood cell, creatinine, glycohemoglobin, atrial fibrillation, blood pressure, and cholesterol (C-index =0.757 [0.726-0.788] and Akaike Information Criterion =7207). When this model was tested in the validation cohort, it performed well in terms of discrimination and calibration abilities (C-index=0.760 [0.693-0.828] and Nam and D'Agostino χ(2) statistic =0.001 for 3 years; C-index=0.782 [0.719-0.846] and Nam and D'Agostino χ(2) statistic=1.037 for 5 years). CONCLUSIONS A risk model based on traditional clinical and biomarkers has a feasible model performance in predicting cardiovascular events in an asymptomatic Korean population.