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.
Level 2 - randomized trial
Individual multicenter double-blind randomized controlled trial
PubMed 31573637 · doi:10.1001/jama.2019.11825
What was done
The CITRIS-ALI trial was a double-blind, placebo-controlled randomized trial across 7 US medical intensive care units enrolling 167 patients with sepsis and ARDS present for less than 24 hours. Patients were randomized to receive intravenous vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water, n = 83) every 6 hours for 96 hours. Primary outcomes were change in modified Sequential Organ Failure Assessment (mSOFA) score from baseline to 96 hours, and plasma C-reactive protein and thrombomodulin levels at 0, 48, 96, and 168 hours.
What was found
No significant differences occurred between vitamin C and placebo groups for primary endpoints: change in mean mSOFA score from baseline to 96 hours went from 9.8 to 6.8 with vitamin C (3.0 points) versus 10.3 to 6.8 with placebo (3.5 points; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86); C-reactive protein at 168 hours was 54.1 vs 46.1 μg/mL (difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33); and thrombomodulin at 168 hours was 14.5 vs 13.8 ng/mL (difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70).
Why it matters
These findings demonstrate that high-dose intravenous vitamin C does not improve organ failure scores or attenuate biomarker evidence of inflammation and endothelial injury in early sepsis-induced ARDS.
Limits
The sample size was modest (n = 167), and only 103 patients (62%) completed the study to day 60. The primary endpoints were restricted to short-term surrogate scores and laboratory markers measured over 7 days rather than long-term clinical endpoints.
Cited by
- context In the CITRIS-ALI trial, patients receiving intravenous vitamin C had fewer ventilator days, spent 7 days in the ICU compared to 10 days for placebo, and had hospital stays approximately one week shorter.
- supports The CITRIS-ALI trial of 167 patients with sepsis and ARDS found 28-day mortality was approximately 30% in the intravenous vitamin C group versus 46% in the placebo group.