Background: Sepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock.
Materials and methods: Our single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay.
Results: Among 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT ( = 45) and the routine ( = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group ( = 0.4, OR 1.19, 95% CI 0.51-2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) ( = 0.03, mean difference -10.84, 95% CI -20.8 to -0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5).
Conclusion: Intravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock.
Clinical significance: HAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock.
How to cite this article: Mohamed ZU, Prasannan P, Moni M, Edathadathil F, Prasanna P, Menon A, Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock. Indian J Crit Care Med 2020;24(8):653-661.
Z. U. Mohamed, Prasannan, P., Moni, M., Edathadathil, F., Prasanna, P., Menon, A., Nair, S., Greeshma C. Ravindran, Sathyapalan, D. T., Menon, V., and Menon, V., “Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock.”, Indian J Crit Care Med, vol. 24, no. 8, pp. 653-661, 2020.