Vitamin C, Hydrocortisone and Thiamine in Patients with Septic Shock (VITAMINS) trial: study protocol and statistical analysis plan

Abstract

Background: Septic shock is associated with poor outcomes. Vitamin C (ascorbic acid) is a cellular antioxidant and has anti-inflammatory properties. Whether the combination therapy of vitamin C, thiamine and hydrocortisone reduces vasopressor dependency in septic shock is unclear. Objectives: To describe the protocol and statistical analysis plan of a multicentre, open-label, prospective, phase 2 randomised clinical trial evaluating the effects of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone monotherapy on the duration of vasopressor administration in critically ill patients with septic shock. Methods: VITAMINS is a multicentre cardiovascular efficacy trial in adult patients with septic shock. Randomisation occurs via a secure website with stratification by site, and allocation concealment is maintained throughout the trial. The primary outcome is the duration of time alive and free of vasopressor administration at Day 7. Secondary outcomes include feasibility endpoints and some patient-centred outcomes. All analyses will be conducted on an intention-to-treat basis. Conclusion: The VITAMINS trial will determine whether combination therapy of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone increases vasopressor-free hours in critically ill patients with septic shock. The conduct of this study will provide important information on the feasibility of studying this intervention in a phase 3 trial.