Corresponding Author: Jonathan E. Sevransky, MD, MHS, Emory University Hospital, Room D226, Atlanta, GA 30322 (jsevran@emory.edu).
Accepted for Publication: January 19, 2021.
Correction: This article was corrected on August 2, 2021, to add the nonauthor collaborators in a supplement.
Author Contributions: Dr Lindsell and Mr Nwosu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Sevransky, Rothman, Hager, Bernard, Buchman, Busse, Coopersmith, DeWilde, Ely, Fowler, Gaieski, Gong, Hall, Hinson, Hooper, Kelen, Khan, Levine, Lewis, Marlin, McGlothlin, Rice, Rudolph, Sanfilippo, Viele, Martin, Wright.
Acquisition, analysis, or interpretation of data: Sevransky, Rothman, Hager, Bernard, Brown, Busse, Coopersmith, DeWilde, Ely, Eyzaguirre, Fowler, Gaieski, Gong, Hall, Hinson, Hooper, Kelen, Khan, Levine, Lewis, Lindsell, Marlin, McGlothlin, Moore, Nugent, Nwosu, Polito, Rice, Ricketts, Viele, Martin, Wright.
Drafting of the manuscript: Sevransky, Rothman, Hager, Bernard, Busse, DeWilde, Ely, Hall, Hinson, Khan, Rice, Rudolph, Viele, Wright.
Critical revision of the manuscript for important intellectual content: Sevransky, Rothman, Hager, Bernard, Brown, Buchman, Busse, Coopersmith, Ely, Eyzaguirre, Fowler, Gaieski, Gong, Hall, Hinson, Hooper, Kelen, Khan, Levine, Lewis, Lindsell, Marlin, McGlothlin, Moore, Nugent, Nwosu, Polito, Rice, Ricketts, Sanfilippo, Viele, Martin, Wright.
Statistical analysis: Ely, Lewis, Lindsell, McGlothlin, Nwosu, Viele.
Obtained funding: Sevransky, Rothman, Bernard, Buchman, Hall, Kelen, Sanfilippo, Wright.
Administrative, technical, or material support: Sevransky, Rothman, Hager, Bernard, Buchman, DeWilde, Ely, Eyzaguirre, Fowler, Gaieski, Hall, Hinson, Hooper, Kelen, Khan, Levine, Lewis, Marlin, Rice, Ricketts, Rudolph, Sanfilippo, Martin, Wright.
Supervision: Sevransky, Rothman, Hager, Bernard, Brown, DeWilde, Ely, Gaieski, Gong, Hall, Hinson, Hooper, Kelen, Khan, Marlin, Nugent, Sanfilippo, Martin, Wright.
Conflict of Interest Disclosures: Dr Sevransky reported receipt of a stipend from Critical Care Medicine for work as an associate editor and grants from the CDC Foundation. Dr Brown reported receipt of personal fees from Hamilton, Oxford University Press/Brigham Young University, and New York University and grants from Faron, Sedana, Janssen, the National Institutes of Health (NIH), and the Department of Defense. Dr Buchman reported that he is senior advisor and intergovernmental personnel assignment to BARDA DRIVe, detailed to the Solving Sepsis program, that he is editor in chief of Critical Care Medicine and Critical Care Explorations, and that he received grants and salary support as site principal investigator for the Surgical Critical Care Initiative managed by the Uniformed Services University of the Health Sciences. Dr Busse reported receipt of speakers bureau fees from La Jolla Pharmaceutical Company. Dr Ely reported receipt of grants from Bioxcel as a trial principal investigator and honoraria for continuing medical education teaching activities from Pfizer and Orion and serving as an unfunded investigator for Eli Lilly. Dr Fowler reported receipt of grants from the National Heart, Lung, and Blood Institute (NHLBI). Dr Gong reported receipt of grants from the NHLBI and the Agency for Healthcare Research and Quality (AHRQ). Dr Hall reported receipt of grants from the Centers for Disease Control and Prevention (CDC), Johnson and Johnson, the NIH, and Nico Corporation. Dr Hinson reported receipt of grants from the AHRQ and the CDC. Dr Khan reported receipt of grants from United Therapeutics, Janssen, Reata Pharma, and the NIH. Dr Lewis reported that he is the senior medical scientist at Berry Consultants LLC, a statistical consulting firm that specializes in adaptive clinical trial design. Dr Lindsell reported receipt of grants from the NIH, the CDC, and the Department of Defense; receipt of research contracts to his institution from Entegrion Inc, Endpoint Health Research, and bioMérieux; and holding stock options in Bioscape Digital; in addition, Dr Lindsell has a patent for risk stratification in pediatric septic shock issued to Cincinnati Children’s Hospital Medical Center. Dr Rice reported consulting for Cumberland Pharmaceuticals Inc, Avisa Pharma LLC, and Cytovale Inc. Dr Martin reported receipt of research advisory board fees from Beckman Coulter, Regeneron, and Grifols. No other disclosures were reported.
Funding/Support: Funding for the trial was provided by the Marcus Foundation to Emory University, which supervised the distribution of resources to clinical sites. Johns Hopkins served as the clinical coordinating center and Vanderbilt University as the data coordinating center. Nova Biomedical Inc provided support to 6 sites with point-of-care glucometers. Vitamin C, thiamine, and hydrocortisone were purchased from McGuff Pharmaceuticals Inc. SCCM Discovery, a critical care research infrastructure program, facilitated the design and conduct of the study, provided administrative support to conducting the study, and was involved in critical manuscript revision. SCCM Discovery reviewed and critiqued the study, which met criteria for SCCM Discovery endorsement.
Role of the Funder/Sponsor: SCCM Discovery was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript. SCCM Discovery was not involved in the approval of the manuscript or the decision to submit the manuscript for publication. The other funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Group Information: For a list of the VICTAS Investigators, see Supplement 5.
Data Sharing Statement: See Supplement 6.
Additional Contributions: We thank Roger J. Lewis, MD, PhD, Harbor-UCLA Medical Center, Jason Connor, PhD, Confluence Stats, R. Phillip Dellinger, MD, Cooper Medical School of Rowan University, Steven Opal, MD, Brown University, and Tiffany M. Osborne, MD, MPH, Washington University, for participation in the trial data and safety monitoring board.