Combined treatment with hydrocortisone, vitamin C, and thiamine for sepsis and septic shock (HYVCTTSSS): A randomized controlled clinical trial.

Abstract Background Whether hydrocortisone, vitamin C, and thiamine treatment can reduce the mortality of patients with sepsis is controversial. Research Question To evaluate the efficacy and safety of hydrocortisone, vitamin C, and thiamine combination treatment for patients with sepsis or septic shock Study Design And Methods This single-blind, randomized controlled trial evaluated treatment with hydrocortisone (50 mg every 6 h for 7 days), vitamin C (1.5 g every 6 h for 4 days), and thiamine (200 mg every 12 h for 4 days) vs placebo (normal saline) in patients with sepsis. The intention-to-treat analysis was used. Primary outcome was 28-day all-cause mortality, and secondary outcomes were organ protection, procalcitonin reduction, and adverse events related to hydrocortisone, vitamin C, and thiamine. Results Eighty patients were randomized to receive combination treatment (n = 40) or normal saline (n = 40). No difference in 28-day all-cause mortality was observed (27.5% vs. 35%; P=0.47), although treatment was associated with a significant improvement of 72-h ΔSOFA score (P = 0.02). In adverse events analysis, the treatment group exhibited more incidents of hypernatremia (P = 0.005). In prespecified subgroup analysis, patients of the treatment subgroup diagnosed with sepsis within 48 h showed lower mortality than those in the control subgroup (p = 0.02). The study was terminated after the mid-term analysis. Interpretation Among patients with sepsis or septic shock, the combination of hydrocortisone, vitamin C, and thiamine did not reduce mortality compared with placebo.