Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial

Sung Yeon Hwang, Jong Eun Park, Ik Joon Jo, Seonwoo Kim, Sung Phil Chung, Taeyoung Kong, Jonghwan Shin, Hui Jai Lee, Kyoung Min You, You Hwan Jo, Doyun Kim, Gil Joon Suh, Taegyun Kim, Won Young Kim, Youn-Jung Kim, Seung Mok Ryoo, Sung-Hyuk Choi, Tae Gun Shin, Korean Shock Society (KoSS) Investigators, Sung Yeon Hwang, Jong Eun Park, Ik Joon Jo, Seonwoo Kim, Sung Phil Chung, Taeyoung Kong, Jonghwan Shin, Hui Jai Lee, Kyoung Min You, You Hwan Jo, Doyun Kim, Gil Joon Suh, Taegyun Kim, Won Young Kim, Youn-Jung Kim, Seung Mok Ryoo, Sung-Hyuk Choi, Tae Gun Shin, Korean Shock Society (KoSS) Investigators

Abstract

Background: Septic shock is a life-threatening condition with underlying circulatory and cellular/metabolic abnormalities. Vitamin C and thiamine are potential candidates for adjunctive therapy; they are expected to improve outcomes based on recent experimental and clinical research. The aim of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial is 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: This study is a randomized, double-blind, placebo-controlled, multicentre trial in adult patients with septic shock recruited from six emergency departments in South Korea. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 116 septic shock patients (58 per group). For the treatment group, vitamin C (50 mg/kg) and thiamine (200 mg) will be mixed in 50 ml of 0.9% saline and administered intravenously every 12 h for a total of 48 h. For the placebo group, an identical volume of 0.9% saline will be administered in the same manner. The primary outcome is the delta Sequential Organ Failure Assessment (SOFA) score (ΔSOFA = initial SOFA at enrolment - follow-up SOFA after 72 h).

Discussion: This trial will provide valuable evidence about the effectiveness of vitamin C and thiamine therapy for septic shock. If effective, this therapy might improve survival and become one of the main therapeutic adjuncts for patients with septic shock.

Trial registration: ClinicalTrials.gov, NCT03756220 . Registered on 5 December 2018.

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

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram
Fig. 2
Fig. 2
Schedule of enrolment, interventions, and assessments. SOFA Sequential Organ Failure Assessment

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