Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients

Adit A. Ginde, Roy G. Brower, Jeffrey M. Caterino, Lani Finck, Valerie M. Banner‑Goodspeed, Colin K. Grissom, Douglas Hayden, Catherine L. Hough, Robert C. Hyzy, Akram Khan, Joseph E. Levitt, Pauline K. Park, Nancy Ringwood, Emanuel P. Rivers, Wesley H. Self, Nathan I. Shapiro, B. Taylor Thompson, Donald M. Yealy, Daniel Talmor

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients.

Original languageEnglish (US)
Pages (from-to)2529-2540
Number of pages12
JournalNew England Journal of Medicine
Volume381
Issue number26
DOIs
StatePublished - Dec 26 2019

Fingerprint

Cholecalciferol
Critical Illness
Vitamins
Placebos
Vitamin D Deficiency
Mortality
Vitamin D
Random Allocation
Small Intestine
Point-of-Care Systems
Confidence Intervals
Calcifediol
Intensive Care Units
Morbidity
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ginde, A. A., Brower, R. G., Caterino, J. M., Finck, L., Banner‑Goodspeed, V. M., Grissom, C. K., ... Talmor, D. (2019). Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients. New England Journal of Medicine, 381(26), 2529-2540. https://doi.org/10.1056/NEJMoa1911124

Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients. / Ginde, Adit A.; Brower, Roy G.; Caterino, Jeffrey M.; Finck, Lani; Banner‑Goodspeed, Valerie M.; Grissom, Colin K.; Hayden, Douglas; Hough, Catherine L.; Hyzy, Robert C.; Khan, Akram; Levitt, Joseph E.; Park, Pauline K.; Ringwood, Nancy; Rivers, Emanuel P.; Self, Wesley H.; Shapiro, Nathan I.; Thompson, B. Taylor; Yealy, Donald M.; Talmor, Daniel.

In: New England Journal of Medicine, Vol. 381, No. 26, 26.12.2019, p. 2529-2540.

Research output: Contribution to journalArticle

Ginde, AA, Brower, RG, Caterino, JM, Finck, L, Banner‑Goodspeed, VM, Grissom, CK, Hayden, D, Hough, CL, Hyzy, RC, Khan, A, Levitt, JE, Park, PK, Ringwood, N, Rivers, EP, Self, WH, Shapiro, NI, Thompson, BT, Yealy, DM & Talmor, D 2019, 'Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients', New England Journal of Medicine, vol. 381, no. 26, pp. 2529-2540. https://doi.org/10.1056/NEJMoa1911124
Ginde AA, Brower RG, Caterino JM, Finck L, Banner‑Goodspeed VM, Grissom CK et al. Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients. New England Journal of Medicine. 2019 Dec 26;381(26):2529-2540. https://doi.org/10.1056/NEJMoa1911124
Ginde, Adit A. ; Brower, Roy G. ; Caterino, Jeffrey M. ; Finck, Lani ; Banner‑Goodspeed, Valerie M. ; Grissom, Colin K. ; Hayden, Douglas ; Hough, Catherine L. ; Hyzy, Robert C. ; Khan, Akram ; Levitt, Joseph E. ; Park, Pauline K. ; Ringwood, Nancy ; Rivers, Emanuel P. ; Self, Wesley H. ; Shapiro, Nathan I. ; Thompson, B. Taylor ; Yealy, Donald M. ; Talmor, Daniel. / Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients. In: New England Journal of Medicine. 2019 ; Vol. 381, No. 26. pp. 2529-2540.
@article{0d6fa630928b4aa3a82a7b6f6176669d,
title = "Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients",
abstract = "BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95{\%} confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5{\%} in the vitamin D group (125 of 531 patients) and 20.6{\%} in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95{\%} CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients.",
author = "Ginde, {Adit A.} and Brower, {Roy G.} and Caterino, {Jeffrey M.} and Lani Finck and Banner‑Goodspeed, {Valerie M.} and Grissom, {Colin K.} and Douglas Hayden and Hough, {Catherine L.} and Hyzy, {Robert C.} and Akram Khan and Levitt, {Joseph E.} and Park, {Pauline K.} and Nancy Ringwood and Rivers, {Emanuel P.} and Self, {Wesley H.} and Shapiro, {Nathan I.} and Thompson, {B. Taylor} and Yealy, {Donald M.} and Daniel Talmor",
year = "2019",
month = "12",
day = "26",
doi = "10.1056/NEJMoa1911124",
language = "English (US)",
volume = "381",
pages = "2529--2540",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "26",

}

TY - JOUR

T1 - Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients

AU - Ginde, Adit A.

AU - Brower, Roy G.

AU - Caterino, Jeffrey M.

AU - Finck, Lani

AU - Banner‑Goodspeed, Valerie M.

AU - Grissom, Colin K.

AU - Hayden, Douglas

AU - Hough, Catherine L.

AU - Hyzy, Robert C.

AU - Khan, Akram

AU - Levitt, Joseph E.

AU - Park, Pauline K.

AU - Ringwood, Nancy

AU - Rivers, Emanuel P.

AU - Self, Wesley H.

AU - Shapiro, Nathan I.

AU - Thompson, B. Taylor

AU - Yealy, Donald M.

AU - Talmor, Daniel

PY - 2019/12/26

Y1 - 2019/12/26

N2 - BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients.

AB - BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients.

UR - http://www.scopus.com/inward/record.url?scp=85077295930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077295930&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1911124

DO - 10.1056/NEJMoa1911124

M3 - Article

C2 - 31826336

AN - SCOPUS:85077295930

VL - 381

SP - 2529

EP - 2540

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 26

ER -