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Author Notes:

Correspondence: dhager1@jhmi.edu

All authors participated in the design and writing of the study protocol.

DNH drafted the manuscript.

DNH, MHH, and GSM revised the manuscript on the basis of input from all other authors.

All authors read and approved the final manuscript.

The authors are deeply indebted to the following individuals for their administrative and scientific support of the VICTAS trial: Lindsay Eyzaguirre, Jessica S. Marlin, Caroline Rudolph, and Fred Sanfilippo, MD, PHD.

EWE reports funding for the VICTAS trial to his institution from the Marcus Foundation and has received honoraria from Pfizer, Orion, and Masimo for continuing medical education activities (no speakers’ bureaus or stocks and so on).

DNH, GRB, AH, JSH, JCJ, REM, and RER report funding for the VICTAS trial to his institution from the Marcus Foundation.

CJL was named as co-inventor on patents related to risk stratification in septic shock.

AM and KV are salaried employees of Berry Consulting, which is under contract with Emory University to support the design work and execution of the VICTAS trial.

DWW reports the grant for the VICTAS trial to his institution from the Marcus Foundation as well as grants from the National Institutes of Health (NIH), the National Highway Transportation Safety Administration, the Department of Defense, NICO Corporation, and the Centers for Disease Control and Prevention.

JES reports grants for the VICTAS trial to his institution from the Marcus Foundation, funding from the Biomedical Advanced Research and Development Authority, and a stipend from the Society of Critical Care Medicine to support his editorial position for the journal Critical Care Medicine.

GSM reports grants for the VICTAS trial to his institution from the Marcus Foundation as well as grants from the NIH and Bristol-Myers Squibb to his institution.

MHH, LWB, ABF, DFG, GDK and ML declare that they have no competing interests.

Subjects:

Research Funding:

Funding for VICTAS was provided by contract to Emory University, the study sponsor, by the Marcus Foundation.

Nova Biomedical provided material support in the form of loaned POC glucometers to some participating sites.

The contact at the sponsoring site is Jonathan Sevransky (jsevran@emory.edu).

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

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

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Journal Title:

Trials

Volume:

Volume 20, Number 1

Publisher:

, Pages 197-197

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2019 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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