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

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Hypovitaminosis 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.


From 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).


Two-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).


Despite 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 (

ABBREVIATIONS DVT = deep vein thrombosis; GCS = Glasgow Coma Scale; ICU = intensive care unit; LOS = length of stay; SAPS II = Simplified Acute Physiology Score; UTI = urinary tract infection.

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Article Information

Correspondence Michael Karsy: Clinical Neurosciences Center, University of Utah, Salt Lake City, UT.


INCLUDE WHEN CITING Published online September 13, 2019; DOI: 10.3171/2018.11.JNS182713.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    CONSORT schematic of clinical trial.

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    Responsiveness to vitamin D supplementation and its impact on LOS for as-treated patients. Asterisk indicates significant difference (p = 0.0001).




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