Journal Article

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

Ely, E. Wesley, Malone, Richard E., Bernard, Gordon R., Hall, Alex, Lindsell, Christopher J., Sevransky, Jonathan E., Rothman, Richard E., Levine, Mark, Wright, David W., Hager, David N., Busse, Laurence W., Gaieski, David F., Jackson, James C., Hooper, Michael H., Viele, Kert, Martin, Greg S., Fowler, Alpha A., Kelen, Gabor D., McGlothlin, Anna, Hinson, Jeremiah S.

2019

Overview

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. Trial registration ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Administration, Intravenous / Animal cognition / Antibiotics / Ascorbic Acid - administration & dosage / Ascorbic Acid - adverse effects / Biomedicine / Clinical trials / Double-Blind Method / Double-blind studies / Drug Administration Schedule / Drug dosages / Drug therapy / Drug Therapy, Combination / Glucocorticoids / Health Sciences / Hospital Mortality / Humans / Hydrocortisone / Hydrocortisone - administration & dosage / Hydrocortisone - adverse effects / Infection / Medicine / Medicine & Public Health / Metabolism / Mortality / Multicenter Studies as Topic / Patients / Permeability / Prospective Studies / Pyrimidines / Quality of life / Randomized Controlled Trials as Topic / Review boards / Risk factors / Sample Size / Sepsis / Sepsis - diagnosis / Sepsis - drug therapy / Sepsis - mortality / Sepsis - physiopathology / Septic shock / Statistics for Life Sciences / Steroids / Steroids (Drugs) / Strategic planning (Business) / Study Protocol / Thiamine / Thiamine - administration & dosage / Thiamine - adverse effects / Time Factors / Treatment Outcome / United States / Vitamin B / Vitamin C / Vitamin deficiency / Vitamins