The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial

• Authors: David N. Hager, Johns Hopkins University; Michael H. Hooper, Eastern Virginia Medical School; Gordon R. Bernard, Vanderbilt University; Laurence Busse, Emory University; E. Wesley Ely, Vanderbilt University; Alpha A. Fowler, Virginia Commonwealth University; David F. Gaieski, Thomas Jefferson University; Alex Hall, Emory University; Jeremiah S. Hinson, Johns Hopkins University; James C. Jackson, Vanderbilt University; Gabor D. Kelen, Johns Hopkins University; Mark Levine, National Institute of Diabetes and Digestive and Kidney Diseases; Christopher J. Lindsell, Vanderbilt University; Richard E. Malone, Vanderbilt University; Anna McGlothlin, Berry Consultants LLC; Richard E. Rothman, Johns Hopkins University; Kert Viele, Berry Consultants LLC; David Wright, Emory University; Jonathan Sevransky, Emory University; Gregory Martin, Emory University
• Journal Title: Trials
• Volume: Volume 20, Number 1
• Publisher: BMC (part of Springer Nature) | 2019-04-05, Pages 197-197
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s13063-019-3254-2
• Subjects: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Medicine, Research & Experimental; Research & Experimental Medicine; Vitamin C; Thiamine; Hydrocortisone; Sepsis; Septic shock; Mortality; Randomized controlled trial; CRITICALLY-ILL PATIENTS; CAMPAIGN INTERNATIONAL GUIDELINES; CONFUSION ASSESSMENT METHOD; SEPTIC SHOCK; ASCORBIC-ACID; CORTICOSTEROID INSUFFICIENCY; OXIDATIVE STRESS; UNITED-STATES; ORGAN FAILURE; HYDROCORTISONE

Abstract

Background: Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed. Methods: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed. Discussion: VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide.