#Grand Rounds

Results from the VITAMINS Trial: Does Combining Hydrocortisone Treatment with Vitamin C and Thiamine Improve Sepsis Outcomes?

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

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

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

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)

< Previous

Next >