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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number197
JournalTrials
Volume20
Issue number1
DOIs
StatePublished - Apr 5 2019

Fingerprint

Thiamine
Sample Size
Ascorbic Acid
Sepsis
Randomized Controlled Trials
Steroids
Placebos
Hydrocortisone
Mortality
Mechanical Ventilators
Random Allocation
Resuscitation
Intensive Care Units
Therapeutics
Anti-Bacterial Agents
Kidney

Keywords

  • Hydrocortisone
  • Mortality
  • Randomized controlled trial
  • Sepsis
  • Septic shock
  • Thiamine
  • Vitamin C

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol : A prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. / Hager, David Northrop; Hooper, Michael H.; Bernard, Gordon R.; Busse, Laurence W.; Ely, E. Wesley; Fowler, Alpha A.; Gaieski, David F.; Hall, Alex; Hinson, Jeremiah; Jackson, James C.; Kelen, Gabor D; Levine, Mark; Lindsell, Christopher J.; Malone, Richard E.; McGlothlin, Anna; Rothman, Richard; Viele, Kert; Wright, David W.; Sevransky, Jonathan E.; Martin, Greg S.

In: Trials, Vol. 20, No. 1, 197, 05.04.2019.

Research output: Contribution to journalArticle

Hager, DN, Hooper, MH, Bernard, GR, Busse, LW, Ely, EW, Fowler, AA, Gaieski, DF, Hall, A, Hinson, J, Jackson, JC, Kelen, GD, Levine, M, Lindsell, CJ, Malone, RE, McGlothlin, A, Rothman, R, Viele, K, Wright, DW, Sevransky, JE & Martin, GS 2019, 'The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: A prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial', Trials, vol. 20, no. 1, 197. https://doi.org/10.1186/s13063-019-3254-2
Hager, David Northrop ; Hooper, Michael H. ; Bernard, Gordon R. ; Busse, Laurence W. ; Ely, E. Wesley ; Fowler, Alpha A. ; Gaieski, David F. ; Hall, Alex ; Hinson, Jeremiah ; Jackson, James C. ; Kelen, Gabor D ; Levine, Mark ; Lindsell, Christopher J. ; Malone, Richard E. ; McGlothlin, Anna ; Rothman, Richard ; Viele, Kert ; Wright, David W. ; Sevransky, Jonathan E. ; Martin, Greg S. / The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol : A prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. In: Trials. 2019 ; Vol. 20, No. 1.
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T1 - The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol

T2 - A prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial

AU - Hager, David Northrop

AU - Hooper, Michael H.

AU - Bernard, Gordon R.

AU - Busse, Laurence W.

AU - Ely, E. Wesley

AU - Fowler, Alpha A.

AU - Gaieski, David F.

AU - Hall, Alex

AU - Hinson, Jeremiah

AU - Jackson, James C.

AU - Kelen, Gabor D

AU - Levine, Mark

AU - Lindsell, Christopher J.

AU - Malone, Richard E.

AU - McGlothlin, Anna

AU - Rothman, Richard

AU - Viele, Kert

AU - Wright, David W.

AU - Sevransky, Jonathan E.

AU - Martin, Greg S.

PY - 2019/4/5

Y1 - 2019/4/5

N2 - 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.

AB - 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.

KW - Hydrocortisone

KW - Mortality

KW - Randomized controlled trial

KW - Sepsis

KW - Septic shock

KW - Thiamine

KW - Vitamin C

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