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Preliminary Communication
Caring for the Critically Ill Patient
October 1, 2019

Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial

Author Affiliations
  • 1Virginia Commonwealth University, Richmond
  • 2Froedtert Hospital and the Medical College of Wisconsin, Milwaukee
  • 3Cleveland Clinic, Cleveland, Ohio
  • 4University of Kentucky, Lexington
  • 5Emory University, Atlanta, Georgia
  • 6Fairview Hospital, Cleveland, Ohio
  • 7Aurora St. Luke's Medical Center, Milwaukee, Wisconsin
JAMA. 2019;322(13):1261-1270. doi:10.1001/jama.2019.11825
Key Points

Question  Can intravenous administration of high-dose vitamin C reduce organ failure scores and biomarkers of inflammation and vascular injury among patients with sepsis and acute respiratory distress syndrome (ARDS)?

Findings  In this randomized clinical trial that included 167 patients in the intensive care unit, intravenous infusion of high-dose vitamin C vs placebo for 96 hours resulted in no significant differences in the modified Sequential Organ Failure Assessment score at 96 hours, or in levels of C-reactive protein and thrombomodulin at 168 hours.

Meaning  Among patients with sepsis and ARDS, high-dose vitamin C infusion compared with placebo did not significantly reduce organ failure scores at 96 hours or improve biomarker levels at 168 hours.

Abstract

Importance  Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).

Objective  To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS.

Design, Setting, and Participants  The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.

Interventions  Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours.

Main Outcomes and Measures  The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.

Results  Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, −0.10; 95% CI, −1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, −8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, −2.8 to 4.2; P = .70) at 168 hours.

Conclusions and Relevance  In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.

Trial Registration  ClinicalTrials.gov Identifier: NCT02106975

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