Intravenous Vitamin C and severe sepsis outcomes

Sepsis and septic shock are caused by a systemic inflammatory response to severe infection that results in multi-organ failure and refractory hypotension.

The incidence of severe sepsis is increasing and is the leading cause of mortality in critically ill patients. Preliminary data indicates that sepsis results in significant depletion of vitamin C levels and a recent Phase I study demonstrated that administration of vitamin C to patients with severe sepsis dramatically improved inflammatory biomarker levels and clinical outcome measures.

Vitamin C acts as a cofactor for numerous regulatory and biosynthetic enzymes, including those responsible for vasopressor synthesis. Therefore, we hypothesise that vitamin C administration will improve sepsis-related disorders such as hypotension through its enzyme cofactor activities.

This Phase II randomised controlled trial will assess the effects of vitamin C infusion on hypotension and vasopressor requirements, as well as markers of oxidative stress, inflammation and leukocyte activity, in patients with severe sepsis. The biochemical mechanisms of action will be determined by measuring a suite of clinically-relevant and novel cofactor activity biomarkers. Overall, this study will establish the efficacy of vitamin C in improving clinical outcomes in the critically ill.