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

Trials

Kert Viele¹  Anna McGlothlin¹  Samuel Nwosu²  Christopher J. Lindsell²  David W. Wright³  Alex Hall³  Richard E. Rothman⁴  Jeremiah S. Hinson⁴  Gabor D. Kelen⁴  David F. Gaieski⁵  Michael H. Hooper⁶  David N. Hager⁷  E. Wesley Ely⁸  Gordon R. Bernard⁸  James C. Jackson⁸  Todd W. Rice⁸  Alpha A. Fowler⁹  Jonathan E. Sevransky^1,10  Laurence W. Busse^1,11  Greg S. Martin^1,12  Mark Levine^1,13 

[1] Berry Consultants, LLC;Department of Biostatistics, Vanderbilt University Medical Center;Department of Emergency Medicine, Emory University;Department of Emergency Medicine, Johns Hopkins University;Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University;Division of Pulmonary & Critical Care Medicine, Department of Medicine, Eastern Virginia Medical School and Sentara Healthcare;Division of Pulmonary & Critical Care Medicine, Department of Medicine, Johns Hopkins University;Division of Pulmonary & Critical Care, Department of Medicine, Vanderbilt University Medical Center;Division of Pulmonary Disease & Critical Care Medicine, Department of Internal Medicine, The VCU Johnson Center for Critical Care and Pulmonary Research, Virginia Commonwealth University School of Medicine;Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University, Emory Critical Care Center;Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University;Grady Memorial Hospital;Molecular & Clinical Nutrition Section, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health;

关键词: Statistical analysis plan;    Adaptive sample size;    Vitamin C;    Thiamine;    Steroids;    Sepsis;   

DOI  :  10.1186/s13063-019-3775-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown