[Source: Journal of American Medical Association, full page: (LINK). Abstract, edited.]
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 III, MD 1; Jonathon D. Truwit, MD 2; R. Duncan Hite, MD 3; Peter E. Morris, MD 4; Christine DeWilde, RN, PhD 1; Anna Priday, BS, MS 1; Bernard Fisher, BS, MS 1; Leroy R. Thacker II, PhD 1; Ramesh Natarajan, PhD 1; Donald F. Brophy, PharmD 1; Robin Sculthorpe, RPh 1; Rahul Nanchal, MD 2; Aamer Syed, MD 1; Jamie Sturgill, PhD 4; Greg S. Martin, MD, MSc 5; Jonathan Sevransky, MD, MHS 5; Markos Kashiouris, MD, MPH 1; Stella Hamman, RN, MSN 1; Katherine F. Egan, BSN, RN, CCRC 5; Andrei Hastings, MD 3; Wendy Spencer, RN, CPN 6; Shawnda Tench, BBA, CCRP 3; Omar Mehkri, MD 3; James Bindas, MBA 3; Abhijit Duggal, MD 3; Jeanette Graf, BS, CCRP 2; Stephanie Zellner, MS, CCRC 2; Lynda Yanny, RN, BSN, CCRC 2; Catherine McPolin, RN, BSN, CCRP 2; Tonya Hollrith, RT, MR 2; David Kramer, MD 2; Charles Ojielo, MD 2; Tessa Damm, DO 7; Evan Cassity, MS 4; Aleksandra Wieliczko, RN 4; Matthew Halquist, PhD 1
Author Affiliations: 1 Virginia Commonwealth University, Richmond; 2 Froedtert Hospital and the Medical College of Wisconsin, Milwaukee; 3 Cleveland Clinic, Cleveland, Ohio; 4 University of Kentucky, Lexington; 5 Emory University, Atlanta, Georgia; 6 Fairview Hospital, Cleveland, Ohio; 7 Aurora St. Luke’s Medical Center, Milwaukee, Wisconsin
JAMA. 2019;322(13):1261-1270. doi:10.1001/jama.2019.11825
- 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.
Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).
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.
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.
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
Keywords: Sepsis; ARDS; Vitamin C; Intensive Care.