Sepsis: high-dose vitamin C trial yields intriguing but uncertain results

  • Fowler AA & al.
  • JAMA
  • 1 Oct 2019

  • International Clinical Digest
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Takeaway

  • When treated with vitamin C, adults with sepsis and acute respiratory distress syndrome (ARDS) do not seem to experience change in organ failure or plasma biomarkers of inflammation and vascular injury. 
  • Many unknowns remain.
  • Editorial : 
    • Mortality difference "is tantalising and likely to spur much debate”.
    • Vitamin C is cheap and safe; larger trials are warranted.

Why this matters

  • Many mechanistic and some trial data suggest vitamin C could be beneficial in sepsis.

Key results

  • Vitamin C vs placebo, change vs baseline in:
    • Modified Sequential Organ Failure Assessment (mSOFA) score (at 96 hours):
      • 3 vs 3.5 points;
      • Difference, −0.10 (P=.86);
    • C-reactive protein (CRP) levels (at 168 hours):
      • 54.1 vs 46.1 μg/mL;
      • Difference, 7.94 μg/mL (P=.33); and
    • Thrombomodulin levels:
      • 14.5 vs 13.8 ng/mL;
      • Difference, 0.69 ng/mL (P=.70).
  • Of 46 prespecified secondary exploratory outcomes, 43 did not differ between groups. 
  • Vitamin C group had significantly lower 28-day mortality, not adjusted for multiple comparisons.

Study design

  • Multicenter, randomised, double-blind, placebo-controlled, proof-of-concept CITRIS-ALI trial (n=167).
  • Participants with sepsis and ARDS were randomly assigned to receive high-dose intravenous vitamin C vs placebo every 6 hours for 96 hours.
  • Outcomes: change in mSOFA score, CRP, thrombomodulin.
  • Funding: NIH; Virginia Commonwealth University.

Limitations

  • ARDS requirement may have delayed vitamin C administration.
  • Small; possibly underpowered.

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