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Author Notes:

Christopher J. Lindsell, Email: chris.lindsell@vumc.org

CJL and SN drafted this statistical analysis plan to execute on the design proposed and described by AM.

All authors provided input on variable definitions, selection of analytical datasets, and approaches to the analysis. All authors read and approved the final manuscript.

CJL takes responsibility for the manuscript.

We would like to thank all contributors to the VICTAS trial, including the many site investigators and members of the steering committee.

In particular, we thank Jessica S. Marlin for her support in operationalizing the variables described in this manuscript, and Fred Sanfillippo for his support in engaging the funding source.

See publication for list of competing interest.

Subjects:

Research Funding:

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

Point-of-care glucometers were loaned to some study sites by Nova Biomedical, which has had no role in the design, execution, or planned analyses of the study, nor the writing of this or future manuscripts.

Keywords:

  • Adaptive sample size
  • Sepsis
  • Septic shock
  • Statistical analysis plan
  • Steroids
  • Thiamine
  • Vitamin C

Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial

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Journal Title:

Trials

Volume:

Volume 20, Number 1

Publisher:

, Pages 670-670

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018.

Copyright information:

© The Author(s). 2019

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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