Methodology: 4/5
Usefulness: 3/5

Fujii T, et al. JAMA. 2020 Jan 17. doi: 10.1001/jama.2019.22176. [Epub ahead of print]

Editorial: Lack of Benefit of High-Dose Vitamin C, Thiamine, and Hydrocortisone Combination for Patients With Sepsis.

Question and Methods: International, multicenter, open-label RCT to determine whether HAT (hydrocortisone, ascorbate, thiamine) compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.

Findings: No difference in main outcome (duration of time alive and free of vasopressor administration up to day 7):

  • Intervention: 122.1 hours (IQR, 76.3-145.4 hours)
  • Control: 124.6 hours (IQR, 82.1-147.0 hours)
  • Though underpowered for mortality/patient-centered outcomes and no adjustment for multiple comparisons, 9/10 secondary outcomes showed no difference


  • Open-label
    Modest sample size (feasibility study)
  • Other markers of quality in sepsis treatment not recorded (time to antibiotics, etc.)
  • Delay of administration of HAT therapy (not a study of early resuscitation)
  • Primary outcome not patient-centered

Interpretation: This trial suggests that HAT therapy did not lead to more rapid resolution of septic shock. There is no immediate justification for adoption of HAT as a component of sepsis treatment. This was not a trial of early resuscitation, with significant delays to administration of HAT therapy. Several trials are ongoing.

By: Dr. Richard Hoang


  • Hans Rosenberg

    Dr. Rosenberg is an emergency physician at the Ottawa Hospital, assistant professor at the University of Ottawa, and Director of the Digital Scholarship and Knowledge Dissemination Program.