Project Details
Projekt
The VICToRY Trial - VItamin C in Thermal injuRY: A feasibility study for a seamless adaptive phase II/III multi-center randomized trial
Applicant
Professor Dr. Christian Stoppe
Subject Area
Anaesthesiology
General and Visceral Surgery
Nutritional Sciences
General and Visceral Surgery
Nutritional Sciences
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 462841520
Background: Worldwide, burn injuries represent a significant public health problem and are ranked the fourth most common injury. Burn patients present with up to a 3-fold higher prevalence of sepsis than other trauma patients. In certain disease states, such as those associated with severe burns and other critical illnesses, the relationship between nutrient deficiencies, altered immune status, and acquired infection has been recognized for many years. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies, thereby predisposing patients to impaired immune function and increased risk of developing infectious complications, organ dysfunction, and death. Consequently, over the last few decades numerous trials have evaluated the impact of different nutrition/nutrient strategies in critically ill patients and in particular, severe burns patients. Recently, there has been renewed interest in the role of high dose intravenous vitamin C supplementation in critically ill patients, as summarized in the proposal. The origins of vitamin C supplementation in burn patients dates back to research done more than 20 years ago and yet, few centers routinely administer high-dose vitamin C to severely burned patients, suggesting that a high level of evidence is warranted. Methods & Aim: we aim to conduct a large-scale, multi-center randomized trial of high-dose intravenous vitamin C. The purpose of the current proposal is to provide the rationale for a feasibility study that, if successful, will lead into a phase II/III multicentre adaptive randomized trial of supplemental intravenous vitamin C. This pilot will be conducted in 90 severe burn injury patients and we aim to evaluate the biological effects of vitamin C (200mg/kg/day x 96 hours) ompared to placebo in severe burn patients by utilizing some features of an adaptive seamless study design, such sample size re-estimation at the end of the phase II component. The feasibility will be judged by a high degree of compliance with the study protocol (>90% compliance with study investigational product (IP), <5% Lost-to-Follow up [LTFU]), low amounts of consent failure (<30%) and contamination (<6%), and adequate enrollment rates to support the larger confirmatory phase II/III trial. We will also use this feasibility pilot study to assess the distribution of Oxidation-reduction potential (ORP) within treated and untreated burn patients measured at 96 h (end of treatment period). These measurements will help us determine if ORP is a suitable primary outcome for the phase II trial and will provide estimates to support sample size determination of the next phase II trial. Conclusion: The purpose of the current proposal is to provide the rationale for a feasibility study that, if successful, will lead into a phase II/III multicentre adaptive randomized trial of supplemental intravenous vitamin C in severe burns patients.
DFG Programme
Clinical Trials
