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Randomized Controlled Trial
. 2020 Nov;46(11):2015-2025.
doi: 10.1007/s00134-020-06191-3. Epub 2020 Aug 11.

Combination therapy of vitamin C and thiamine for septic shock: a multi-centre, double-blinded randomized, controlled study

Sung Yeon Hwang #  1 , Seung Mok Ryoo #  2 , Jong Eun Park  1 , You Hwan Jo  3   4 , Dong-Hyun Jang  3   4 , Gil Joon Suh  4 , Taegyun Kim  4 , Youn-Jung Kim  2 , Seonwoo Kim  5 , Hyun Cho  5 , Ik Joon Jo  1 , Sung Phil Chung  6 , Sung-Hyuk Choi  7 , Tae Gun Shin #  8 , Won Young Kim #  9 ; Korean Shock Society (KoSS)
Affiliations
Randomized Controlled Trial

Combination therapy of vitamin C and thiamine for septic shock: a multi-centre, double-blinded randomized, controlled study

Sung Yeon Hwang et al. Intensive Care Med. 2020 Nov.

Abstract

Purpose: To evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock.

Methods: The ascorbic acid and thiamine effect in septic shock (ATESS) trial was a multi-centre, double-blind, randomized, controlled trial conducted in four academic emergency departments, enrolling adult patients with septic shock from December 2018 through January 2020. Patients were randomly assigned in a 1:1 ratio to either the treatment group [intravenous vitamin C (50 mg/kg, maximum single dose 3 g) and thiamine (200 mg) administration every 12 h for a total of 48 h] or the placebo group (identical volume of 0.9% saline with the same protocol). The primary outcome was Δ Sequential Organ Failure Assessment (SOFA) score (SOFA score at enrolment-SOFA score after 72 h). Eighteen secondary outcomes were predefined, including shock reversal and 28-day mortality.

Results: A total of 111 patients were enrolled, of which 53 were assigned to the treatment group and 58 were assigned to the placebo group. There was no significant difference in ΔSOFA scores between the treatment group and the placebo group [3, interquartile range (IQR) - 1 to 5 vs. 3, IQR 0-4, respectively, p = 0.96]. Predefined secondary outcomes were also not significantly different between the groups.

Conclusion: In this study, vitamin C and thiamine administration in the early phase of septic shock did not improve organ function compared with placebo, despite improvements in vitamin C and thiamine levels.

Keywords: Resuscitation; Sepsis; Septic shock; Thiamine; Vitamin C.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Serum levels and deficiency rates of vitamin C and thiamine during the first 72 h from enrolment: a vitamin C levels, b thiamine levels, c vitamin C deficiency rate, d thiamine deficiency rate. The median vitamin C levels in the treatment and placebo groups were 10.6 μmol/L (IQR 6–20.6; n = 53) vs. 11.5 μmol/L (IQR 5–24.1; n = 57) at enrolment (p = 0.72) and 44 μmol/L (IQR 33.2–72.4; n = 49) vs. 9 μmol/L (IQR 3.7–16.9; n = 56) at 72 h (p < 0.01). The median thiamine levels in the treatment group and the placebo group were 133.4 nmol/L (IQR 86–181.5; n = 53) vs. 151.2 nmol/L (IQR 124.7–221.6; n = 57) at enrolment (p = 0.1) and 282.6 nmol/L (IQR 210.1–337; n = 49) vs. 125.6 nmol/L (IQR 94.8–167.6; n = 56) at 72 h (p < 0.01). Vitamin C deficiency was defined as vitamin C level < 11.4 μmol/L, and thiamine deficiency was defined as thiamine level < 66.1 nmol/L. There was a significant difference in vitamin C deficiency between the two groups at 72 h (0% in the treatment group vs. 55.4% in the placebo group; p < 0.01). IQR, interquartile range
Fig. 3
Fig. 3
Kaplan–Meier analysis for mortality and shock reversal
See this image and copyright information in PMC

Comment in

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