IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial*

Abstract

OBJECTIVES: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. DESIGN: Bayesian reanalysis of a randomized placebo-controlled trial. SETTING: Thirty-five ICUs. PATIENTS: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. INTERVENTIONS: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04–1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00–1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97–1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98–1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94–1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92–1.19; probability of harm, 76%) priors. CONCLUSIONS: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.