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

Alpha A. Fowler, Jonathon D. Truwit, R. Duncan Hite, Peter E. Morris, Christine Dewilde, Anna Priday, Bernard Fisher, Leroy R. Thacker, Ramesh Natarajan, Donald F. Brophy, Robin Sculthorpe, Rahul Nanchal, Aamer Syed, Jamie Sturgill, Greg S. Martin, Jonathan Sevransky, Markos Kashiouris, Stella Hamman, Katherine F. Egan, Andrei HastingsWendy Spencer, Shawnda Tench, Omar Mehkri, James Bindas, Abhijit Duggal, Jeanette Graf, Stephanie Zellner, Lynda Yanny, Catherine McPolin, Tonya Hollrith, David Kramer, Charles Ojielo, Tessa Damm, Evan Cassity, Aleksandra Wieliczko, Matthew Halquist

Research output: Contribution to journalArticlepeer-review

655 Scopus citations

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.

Original languageEnglish
Pages (from-to)1261-1270
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume322
Issue number13
DOIs
StatePublished - Oct 1 2019

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© 2019 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • General Medicine

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