Combined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial

Abstract

Whether hydrocortisone, vitamin C, and thiamine treatment can reduce the mortality of patients with sepsis is controversial. To evaluate the efficacy and safety of hydrocortisone, vitamin C, and thiamine combination treatment for patients with sepsis or septic shock (HYVCTTSSS). This single-blind, randomized controlled trial evaluated treatment with hydrocortisone (50mg every 6 h for 7days), vitamin C (1.5g every 6h for 4days), and thiamine (200mg every 12h for 4days) vsplacebo (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. 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%vs35%, respectively; P= .47); however, treatment was associated with a significant improvement of 72-h change in Sequential Organ Failure Assessment score (P= .02). In adverse events analysis, the treatment group exhibited more incidents of hypernatremia (P= .005). In prespecified subgroup analysis, patients of the treatment subgroup diagnosed with sepsis within 48h showed lower mortality than those in the control subgroup (P= .02). The study was terminated after the midterm analysis. Among patients with sepsis or septic shock, the combination of hydrocortisone, vitamin C, and thiamine did not reduce mortality compared with placebo. ClinicalTrials.gov; No.: NCT03258684; URL: www.clinicaltrials.gov.