Alpha A. Fowler , Jonathon D. Truwit , R. Duncan Hite et el published results of CITRIS-ALI trial in JAMA on Oct1, 2019.
WHAT
It was a randomized double blind placebo controlled multi Center trial conducted in 7 medical ICUs in the USA, comparing placebo to vitamin-C infusion( 50 milligram/kilogram, every 6 hours for 96 hours) in patients with sepsis and ARDS who were receiving mechanical ventilation. Purpose of trial was to assess the effect of vitamin-C on inflammation and vascular injury.
OUTCOMES
Primary outcomes were change in modified sequential organ failure assessment score(SOFA, range 0-20), bio markers of inflammation C reactive protein and vascular injury ( thrombomodulin levels).
There were several secondary outcomes including 28 day mortality.
RESULTS
There were no significant differences between vitamin c and placebo groups in the primary outcomes.
In exploratory analysis of 46 specified secondary out comes, 3 secondary outcomes were significantly different between groups.
- At 28 day, mortality was 46.3% in the placebo group versus 29.8% in the vitamin-C group.
- Number ventilator free days were 13.1 and vitamin-C group versus 10.6 in placebo.
- Number of ICU free days 10.7 in vitamin-C group versus 7.7 in placebo group.
DISCUSSION
Since early 17 Century, when James Lind discovered that Sailors who received citrus fruits recovered from scurvy, vitamin-C has been proposed or thought to be speed recovery from influenza, common cold, cancer etc.
Researchers have been advocating vitamin C as treatment for sepsis, and recently a before after trial of vitamin-C showed promising results in sepsis.
Physiologically, vitamin-C is crucial for endogenous synthesis of catecholamines. In laboratory, vitamin-C ameliorate cytokine surges implicated in sepsis induced organ dysfunction.
This trial demonstrated that there was no difference in mediators of inflammation and organ dysfunction when treated with vitamin-C. Furthermore, vitamin-C was well tolerated and vitamin C levels improved with the treatment.
In secondary analyses, 28 day of mortality, ventilator free day were better in vitamin-C treated group. Surprisingly, other secondary outcomes, which are closely linked to mortality or inflammation were not different. the finding of reduce mortality was without adjustment for multiple comparisons.
Mortality benefit seen in secondary analysis justifies the need for a larger trial, does not provide a conclusive proof of its effectiveness. Hopefully, such a trial will look at mortality benefit as primary outcome.