Julie Menard, Ruxandra Pinto, Deborah J Cook, Andrew G. Day, Shay P. McGuinness, Dian Cohen, Rebecca Porteous, Elaine Carbonneau, France Clarke, David M. Maslove, Miranda Hunt, Martine Lebrasseur, Sangeeta Mehta, Hector Quiroz-Martinez, Remi LeBlanc, Gordon Wood, Jason Shahin, Bharath-Kumar Tirupakuzhi Vijayaraghavan, Brigitte Bolduc, Nicole Marinoff, Tina Millen, Maureen O. Meade, Lori Hand, Michaël Chassé, Andrew J.E. Seely, Neill K.J. Adhikari, François Lamontagne, Marie-Hélène Masse, Sheila Sprague, Daren K. Heyland, Marie-Claude Battista, Gordon H. Guyatt, Salmaan Kanji, Rachael Parke, Yaseen M. Arabi, Bram Rochwerg, Irene Watpool, Frederick D’Aragon, Emilie P. Belley-Cote, François Lauzier, Oleksa G. Rewa, Demetrios J. Kutsogiannis, Armand Mekontso-Dessap, Tina S. Mele, Alexis F. Turgeon, Sandeep S. Kohli, Pawel Twardowski, Djillali Annane, Paul J. Young, Emmanuel Charbonney

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.).