Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, 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, Jay S Steingrub, Mark Tidswell, Lori-Ann Kozikowski, Lesley De Souzaa, Cynthia Kardos, Nicholas S Hill, Veronica Bacong, Omar Shweish, Haval Chweich, Erik Garpestad, Peter Hou, Rebecca Baron, Anthony Massaro, Laura Fredenburgh, Imoigele Aisiku, Raghu Seethala, Jeffrey Skubic, Arman Isrealyan, Lauren Precopio, Meghan Fawcett, Sarah Pajak, Richard Riker, Adelene MacLeod, Theresa May, Thomas Van der Kloot, David Seder, Daniel Talmor, Nathan Shapiro, Valerie Banner-Goodspeed, Sharon Hayes, Ted Raddell, Kathryn A Hibbert, Michael Filbin, Kelsey Brait, Melissa Stathas, Caroline Rizzo, Patricia A Arsenault, Pam Sigel, David Miru, Alan E Jones, John R Spurzem, Michael A Puskarich, Jasmine McDonald, Maggie Kirby, Michael Matthay, Kathleen Liu, Carolyn S Calfee, Jeff Gotts, Amy Ni, Kathryn Vessel, Annika Belzer, Eyad Almarsi, Janna Blaauw, Alyssa Hughes, Kyndra Sousa, Patil Armenian, Timothy E Albertson, Brian Morrissey, Skyler J Pearson, Maya Juarez, James Chenoweth, Joe Levitt, Jenny Wilson, Angela Rogers, Rosemary Vojnik, Jonasel Roque, Gregory W Hendey, Steven Y Chang, Nida Qadir, Bryan Garber, Christopher Phan, Adit Ginde, Marc Moss, Lani Finck, Sarah Perman, Jean Hoffman, Katherine Mayer, Ivor Douglas, Jason Haukoos, Terra Hiller, Carolynn Lyle, Judy Oakes, Emily Caruso, Meggan Schmidt, Stephanie Gravitz, David Van Pelt, Jeff McKeehan, Carrie Higgins, James Finigan, Ryan Paterson, Kenneth Lyn-Kew, Michelle Howell, Robert C Hyzy, Pauline K Park, Kristine Nelson, Ivan N Co, Jake I McSparron, Kyle J Gunnerson, Tina Chen, Sinan Hanna, Norman Olbrich, Emmanuel P Rivers, Jayna Gardner Gray, Bruno DiGiovine, Jasreen Kaur Gill, Aaron Cook, Kaleem Chaudry, Jacqueline Day, Sarah Rubino, Anja Kathrina Jaehne, Jacqueline Pflaum, Gina Hurst, Jennifer Swiderek, Namita Jayaprakesh, Michelle Ng Gong, Aluko Hope, Swarna Gummadi, Lynne D Richardson, Samuel Acquah, Mark Andreae, Kusum Mathews, Neha Goel, Cindy Clesca, Natalie S Massenburg, Jen-Ting Chen, Brenda Lopez, Michael Aboodi, R Duncan Hite, Abhijit Duggal, Sharon Mace, Andrei Hastings, Omar Mehkri, Stephanie Stoianoff, Thomas E Terndrup, Matthew C Exline, Joshua A Englert, Sarah C Karow, Joshua Garmatter, Kristin Hudock, Ope Adeoye, David Norton, Autumn Studer, Kari Gorder, D Mark Courtney, Megan Rowland, Catherine L Hough, Bryce R H Robinson, Nicholas J Johnson, Stephanie Gundel, Sarah Katsandres, Daniel Henning, Tzevan Poon, Sarah Dean, Jennifer Cardey, Anna Ungar, D Shane O'Mahony, Julie Wallick, Akram Khan, Martin Schreiber, Bory Kea, Ebaad Haq, Olivia Krol, Derek C Angus, Donald M Yealy, David T Huang, Bryan J McVerry, Caroline Gacka, Joseph Yanta, Michael Abesamis, Sarah L McGarry, Jordan Schooler, Margaret Wojnar, Elizabeth Sinz, Christopher Zacko, Nancy Campbell, D Clark Files, Chadwick Miller, Kevin Gibbs, Lori Flores, Lauren Koehler, Kyle Enfield, Mark Sochor, Mary Marshall, Ashley Simpson, Desmarie Sherwood, Marjolein de Wit, Stephen Miller, Aamer Syed, Jessica Mason, Stella Hamman, Peter Morris, Roger Humphries, Jamie Sturgill, Ashley Montgomery-Yates, Evan P Cassity, Samuel M Brown, Joseph Bledsoe, Ithan Peltan, Michael Lanspa, Katie Brown, Brent Armbruster, Quinn Montgomery, Valerie Aston, Eliotte Hirshberg, Dixie Harris, Wayne Woodard, Naresh Kumar, Mardee Merrill, David Nielson, Austin Daw, Estelle Harris, Robert Paine, Amber Plante, Elizabeth Middleton, Wesley H Self, Todd W Rice, Matthew W Semler, Adrienne Baughman, Margaret Hays, Karen Miller, Susan Mogan, David R Janz, Paula Lauto, Margaret M Moore, Bennett P deBoisblanc, John P Hunt, Shannon S Carson, Timothy F Platts-Mills, Eugenia B Quackenbush, Kevin J Chronowski, Colleen Rice, Alexander T Limkakeng Jr, S Michelle Griffin, J Clancy Leahy, Christopher Cox, John Eppensteiner, David A Schoenfeld, B Taylor Thompson, Kathleen Tiffany Lee, Christine Ulysse, Cathryn F Oldmixon, Nancy J Ringwood, Jenna R Pedrin, Richard E Morse, Douglas Hayden, Roy G Brower, Karen Bienstock, Carol J Blaisdell, Michelle Freemer, Andrea L Harabin, Lauren Kunz, Lora A Reineck, Peyvand Ghofrani, Myron A Waclawiw, Gail Weinmann, Laurie J Morrison, Charles B Cairns, Mark N Gillespie, Richard J Kryscio, Damon Scales, Polly Parsons, Jason D Christie, Jesse R Hall, Nicholas J Horton, Jeffrey A Kline, Mitchell Levy, Mark Siegel, Ian Stiell, Laurie S Zoloth, National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, 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, Jay S Steingrub, Mark Tidswell, Lori-Ann Kozikowski, Lesley De Souzaa, Cynthia Kardos, Nicholas S Hill, Veronica Bacong, Omar Shweish, Haval Chweich, Erik Garpestad, Peter Hou, Rebecca Baron, Anthony Massaro, Laura Fredenburgh, Imoigele Aisiku, Raghu Seethala, Jeffrey Skubic, Arman Isrealyan, Lauren Precopio, Meghan Fawcett, Sarah Pajak, Richard Riker, Adelene MacLeod, Theresa May, Thomas Van der Kloot, David Seder, Daniel Talmor, Nathan Shapiro, Valerie Banner-Goodspeed, Sharon Hayes, Ted Raddell, Kathryn A Hibbert, Michael Filbin, Kelsey Brait, Melissa Stathas, Caroline Rizzo, Patricia A Arsenault, Pam Sigel, David Miru, Alan E Jones, John R Spurzem, Michael A Puskarich, Jasmine McDonald, Maggie Kirby, Michael Matthay, Kathleen Liu, Carolyn S Calfee, Jeff Gotts, Amy Ni, Kathryn Vessel, Annika Belzer, Eyad Almarsi, Janna Blaauw, Alyssa Hughes, Kyndra Sousa, Patil Armenian, Timothy E Albertson, Brian Morrissey, Skyler J Pearson, Maya Juarez, James Chenoweth, Joe Levitt, Jenny Wilson, Angela Rogers, Rosemary Vojnik, Jonasel Roque, Gregory W Hendey, Steven Y Chang, Nida Qadir, Bryan Garber, Christopher Phan, Adit Ginde, Marc Moss, Lani Finck, Sarah Perman, Jean Hoffman, Katherine Mayer, Ivor Douglas, Jason Haukoos, Terra Hiller, Carolynn Lyle, Judy Oakes, Emily Caruso, Meggan Schmidt, Stephanie Gravitz, David Van Pelt, Jeff McKeehan, Carrie Higgins, James Finigan, Ryan Paterson, Kenneth Lyn-Kew, Michelle Howell, Robert C Hyzy, Pauline K Park, Kristine Nelson, Ivan N Co, Jake I McSparron, Kyle J Gunnerson, Tina Chen, Sinan Hanna, Norman Olbrich, Emmanuel P Rivers, Jayna Gardner Gray, Bruno DiGiovine, Jasreen Kaur Gill, Aaron Cook, Kaleem Chaudry, Jacqueline Day, Sarah Rubino, Anja Kathrina Jaehne, Jacqueline Pflaum, Gina Hurst, Jennifer Swiderek, Namita Jayaprakesh, Michelle Ng Gong, Aluko Hope, Swarna Gummadi, Lynne D Richardson, Samuel Acquah, Mark Andreae, Kusum Mathews, Neha Goel, Cindy Clesca, Natalie S Massenburg, Jen-Ting Chen, Brenda Lopez, Michael Aboodi, R Duncan Hite, Abhijit Duggal, Sharon Mace, Andrei Hastings, Omar Mehkri, Stephanie Stoianoff, Thomas E Terndrup, Matthew C Exline, Joshua A Englert, Sarah C Karow, Joshua Garmatter, Kristin Hudock, Ope Adeoye, David Norton, Autumn Studer, Kari Gorder, D Mark Courtney, Megan Rowland, Catherine L Hough, Bryce R H Robinson, Nicholas J Johnson, Stephanie Gundel, Sarah Katsandres, Daniel Henning, Tzevan Poon, Sarah Dean, Jennifer Cardey, Anna Ungar, D Shane O'Mahony, Julie Wallick, Akram Khan, Martin Schreiber, Bory Kea, Ebaad Haq, Olivia Krol, Derek C Angus, Donald M Yealy, David T Huang, Bryan J McVerry, Caroline Gacka, Joseph Yanta, Michael Abesamis, Sarah L McGarry, Jordan Schooler, Margaret Wojnar, Elizabeth Sinz, Christopher Zacko, Nancy Campbell, D Clark Files, Chadwick Miller, Kevin Gibbs, Lori Flores, Lauren Koehler, Kyle Enfield, Mark Sochor, Mary Marshall, Ashley Simpson, Desmarie Sherwood, Marjolein de Wit, Stephen Miller, Aamer Syed, Jessica Mason, Stella Hamman, Peter Morris, Roger Humphries, Jamie Sturgill, Ashley Montgomery-Yates, Evan P Cassity, Samuel M Brown, Joseph Bledsoe, Ithan Peltan, Michael Lanspa, Katie Brown, Brent Armbruster, Quinn Montgomery, Valerie Aston, Eliotte Hirshberg, Dixie Harris, Wayne Woodard, Naresh Kumar, Mardee Merrill, David Nielson, Austin Daw, Estelle Harris, Robert Paine, Amber Plante, Elizabeth Middleton, Wesley H Self, Todd W Rice, Matthew W Semler, Adrienne Baughman, Margaret Hays, Karen Miller, Susan Mogan, David R Janz, Paula Lauto, Margaret M Moore, Bennett P deBoisblanc, John P Hunt, Shannon S Carson, Timothy F Platts-Mills, Eugenia B Quackenbush, Kevin J Chronowski, Colleen Rice, Alexander T Limkakeng Jr, S Michelle Griffin, J Clancy Leahy, Christopher Cox, John Eppensteiner, David A Schoenfeld, B Taylor Thompson, Kathleen Tiffany Lee, Christine Ulysse, Cathryn F Oldmixon, Nancy J Ringwood, Jenna R Pedrin, Richard E Morse, Douglas Hayden, Roy G Brower, Karen Bienstock, Carol J Blaisdell, Michelle Freemer, Andrea L Harabin, Lauren Kunz, Lora A Reineck, Peyvand Ghofrani, Myron A Waclawiw, Gail Weinmann, Laurie J Morrison, Charles B Cairns, Mark N Gillespie, Richard J Kryscio, Damon Scales, Polly Parsons, Jason D Christie, Jesse R Hall, Nicholas J Horton, Jeffrey A Kline, Mitchell Levy, Mark Siegel, Ian Stiell, Laurie S Zoloth
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. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).
Copyright © 2019 Massachusetts Medical Society.
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Source: PubMed