Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction.
In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.
A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P=0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event.
In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.)
Funding and Disclosures
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Drs. Lamontagne and Adhikari contributed equally to this article.
This article was published on June 15, 2022, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank the trial patients and their caregivers; the health care providers, research and laboratory staff members, and trial and data coordinators; the staff members at the Unité de Recherche Clinique et Épidémiologique of the Centre de Recherche du CHU de Sherbrooke for providing support in the conduct of the trial; Louise Robert Petit for her work with biologic specimens and supplies; Marie-Pier Domingue for her assistance in the preparation of earlier versions of the figures; Anitra Carr for her insights regarding the potential underlying mechanisms of the effects of vitamin C in previous studies; members of the Canadian Critical Care Trials Group for their input on methodologic issues, including Ron Wald for his review of the manuscript; and the members of the data and safety monitoring board (Andreas Laupacis, Lauren Griffith, and Scott Halpern); and the broader Code C community, whose support proved essential to the success of this trial.
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