Effect of #VitaminC Infusion on Organ Failure and #Biomarkers of #Inflammation and #Vascular Injury in Patients With #Sepsis and #ARDS – The CITRIS-ALI #RCT (JAMA, Abstract)

[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
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

Keywords: Sepsis; ARDS; Vitamin C; Intensive Care.

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#Vitamin C potentiates the killing of #Mycobacterium tuberculosis by the first-line #tuberculosis drugs #isoniazid and #rifampicin in mice (J Antimicrob Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice

Catherine Vilchèze,  John Kim and  William R. Jacobs Jr*

Author Affiliations: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

 

ABSTRACT

The treatment of drug-susceptible tuberculosis (TB) is long and cumbersome. Mismanagement of TB treatment can lead to the emergence of drug resistance in patients, so shortening the treatment duration could significantly improve TB chemotherapy and prevent the development of drug resistance. We had previously discovered that high concentrations of vitamin C sterilize cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis. Here, we tested sub-inhibitory concentration of vitamin C in combination with TB drugs against M. tuberculosis in vitro and in a mouse model of M. tuberculosis infection. In vivo, we showed that vitamin C level in mouse serum can be increased by intraperitoneal injection of vitamin C to reach vitamin C levels close to the concentrations required for activity in vitro. Although vitamin C had no activity by itself in M. tuberculosis-infected mice, the combination of vitamin C with the first-line TB drugs isoniazid and rifampicin reduced the bacterial burden in the lungs of M. tuberculosis-infected mice faster than isoniazid and rifampicin combined in two independent experiments. These experiments suggest that the addition of vitamin C to first-line TB drugs could shorten TB treatment. Vitamin C, an inexpensive and non-toxic compound, could be easily added to the TB pharmacopeia to substantially improve chemotherapy outcome, which would have a significant impact on the worldwide TB community.

 

FOOTNOTES

*Corresponding author. Tel: (718) 678-1075; Fax: (718) 678-1085; E-mail: jacobsw@hhmi.org

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Tuberculosis; Antibiotics; Vitamic C; Isoniazid; Rifampicin.

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