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

Limitations:

  • 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.