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