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

Chest. 2020 Jul;158(1):174-182. doi: 10.1016/j.chest.2020.02.065. Epub 2020 Mar 31.


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 (HYVCTTSSS).

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%, 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 48 h showed lower mortality than those in the control subgroup (P = .02). The study was terminated after the midterm analysis.

Interpretation: Among patients with sepsis or septic shock, the combination of hydrocortisone, vitamin C, and thiamine did not reduce mortality compared with placebo.

Trial registry:; No.: NCT03258684; URL:

Keywords: HYVCTTSSS; hydrocortisone; sepsis; thiamine; vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Critical Care
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrocortisone / therapeutic use*
  • Male
  • Middle Aged
  • Organ Dysfunction Scores
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Single-Blind Method
  • Survival Rate
  • Thiamine / therapeutic use*
  • Vitamins / therapeutic use*


  • Anti-Inflammatory Agents
  • Vitamins
  • Ascorbic Acid
  • Hydrocortisone
  • Thiamine

Associated data