The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY)

Abstract

OBJECTIVEHypovitaminosis D is prevalent in neurocritical care patients, but the potential to improve patient outcome by replenishing vitamin D has not been investigated. This single-center, double-blinded, placebo-controlled, randomized (1:1) clinical trial was designed to assess the effect on patient outcome of vitamin D supplementation in neurocritical care patients with hypovitaminosis D.METHODSFrom October 2016 until April 2018, emergently admitted neurocritical care patients with vitamin D deficiency (≤ 20 ng/ml) were randomized to receive vitamin D3 (cholecalciferol, 540,000 IU) (n = 134) or placebo (n = 133). Hospital length of stay (LOS) was the primary outcome; secondary outcomes included intensive care unit (ICU) LOS, repeat vitamin D levels, patient complications, and patient disposition. Exploratory analysis evaluated specific subgroups of patients by LOS, Glasgow Coma Scale (GCS) score, and Simplified Acute Physiology Score (SAPS II).RESULTSTwo-hundred seventy-four patients were randomized (intent-to-treat) and 267 were administered treatment within 48 hours of admission (as-treated; 61.2% of planned recruitment) and monitored. The mean age of as-treated patients was 54.0 ± 17.2 years (56.9% male, 77.2% white). After interim analysis suggested a low conditional power for outcome difference (predictive power 0.12), the trial was halted. For as-treated patients, no significant difference in hospital LOS (10.4 ± 14.5 days vs 9.1 ± 7.9 days, p = 0.4; mean difference 1.3, 95% CI −1.5 to 4.1) or ICU LOS (5.8 ± 7.5 days vs 5.4 ± 6.4 days, p = 0.4; mean difference 0.4, 95% CI −1.3 to 2.1) was seen between vitamin D3 and placebo groups, respectively. Vitamin D3 supplementation significantly improved repeat serum levels compared with placebo (20.8 ± 9.3 ng/ml vs 12.8 ± 4.8 ng/ml, p < 0.001) without adverse side effects. No subgroups were identified by exclusion of LOS outliers or segregation by GCS score, SAPS II, or severe vitamin D deficiency (≤ 10 ng/ml).CONCLUSIONSDespite studies showing that vitamin D can predict prognosis, supplementation in vitamin D–deficient neurocritical care patients did not result in appreciable improvement in outcomes and likely does not play a role in acute clinical recovery.Clinical trial registration no.: NCT02881957 (clinicaltrials.gov)

Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials

“…Several randomized controlled trials (RCTs) were conducted to investigate the effects of vitamin D supplementation on the outcomes of critically ill patients. However, their results are conflicting [19][20][21][22][23][24][25][26][27][28] . Some studies showed that vitamin D supplementation demonstrated positive effects by decreasing the length of hospital stay 23 , duration of mechanical ventilation (MV) 26,27 , and mortality rate 24,27 .…”

Association between Vitamin D supplementation and mortality in critically ill patients: A systematic review and meta-analysis of randomized clinical trials

“…eTable 6 in S1 Appendix shows the support for judgment for included trials rated as high or unclear risk of bias. All trials had a low risk of bias [10,17,[21][22][23][24][25][26][27]. Key findings of GRADE assessment of certainty for all outcomes are presented in eTable 4 in S1 Appendix.…”

“…Seven trials [5,8,10,[17][18][19][20] reported length of hospital stay, and seven trials [5,6,8,10,17,19,20] reported the length of ICU stay. One thousand thirteen patients take vitamin D and 983…”

“…Observational studies have indicated that vitamin D deficiency is common in critically ill patients and is associated with mortality and length of ICU stay [3,4]. Early randomized clinical trials (RCTs) individual showed lower observed mortality than placebo, although the differences were not significant [5][6][7][8][9][10]. In 2017 and 2018, three systematic reviews [11][12][13] have discussed the association between vitamin D supplementation and the most important clinical outcomes: all-cause mortality.…”

“…One review [ 12 ] has shown benefit of vitamin D on survival, while two reviews [ 11 , 13 ] have not shown the benefit. The ongoing debate has been fueled by the recent publications, two large RCTs [ 5 , 14 ]. Thus, we performed a systematic review and meta-analysis to assess the effect of vitamin D compared to placebo on mortality.…”