BACKGROUND AND PURPOSE:

• Vitamin C has been studied, due to its anti-inflammatory and antioxidant properties, as a possible addition to sepsis protocols
  • Thiamine has been included in some protocols due to frequency of thiamine deficiency in patients with sepsis
• Fujii et al. (JAMA, 2020) assessed whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock

METHODS:

• Multicenter, open-label, randomized clinical trial (RCT)
  • Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock (VITAMINS)
• Participants
  • Patients in septic shock
• Randomization arms
  • Intervention group
    • Intravenous vitamin C (1.5 g every 6 hours) | Hydrocortisone (50 mg every 6 hours) | Thiamine (200 mg every 12 hours)
  • Control group
    • Intravenous hydrocortisone (50 mg every 6 hours) alone
• Study design
  • Treatment continued until shock resolution or up to 10 days
• Primary outcome
  • Duration of time alive and free of vasopressor administration up to day 7
• Secondary outcomes
  • 28-day, 90-day, ICU, and hospital mortality | 28-day cumulative vasopressor-free days, mechanical ventilation-free days, renal replacement therapy–free days | Change in SOFA score at day 3 | 28-day ICU free-days | Hospital length of stay

RESULTS:

• 216 patients were randomized | 109 to intervention group | 107 to control group
  • Mean age: 61.7 years
• Primary outcome: Time alive and vasopressor free up to day 7
  • Intervention group: 122.1 hours
  • Control group: 124.6 hours
• The median difference was not statistically significant (–0.6 hours ; P = 0.83)
• Of the prespecified secondary outcomes the only difference seen was in the change in median SOFA score at day 3
  • Intervention group: –2
  • Control group: –1
  • Difference: –1.0 (95% CI, –1.9 to –0.1; P = .02)
• Serious adverse events or suspected unexpected serious events: None reported

CONCLUSION:

• Treatment with a vitamin C, hydrocortisone, and thiamine in combination did not improve sepsis outcomes
• Improvement in SOFA score should be interpreted with caution | Potential for bias for competing risks in opposite directions (patients who were healthier would have been discharged from the ICU and not accounted for)

Learn More – Primary Sources:

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock – The VITAMINS Randomized Clinical Trial

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