Vitamin C, Thiamine and Hydrocortisone for the Treatment of Septic Shock

Initiation of Vitamin C, Thiamine and Hydrocortisone Therapy for Septic Shock in Adults: A Randomized Clinical Trial

The purpose of this study is to determine whether the combination therapy (vitamin C,thiamine and hydrocortisone) is effective in the treatment of septic shock.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin C,thiamine,hydrocortisone

Detailed Description

Septic Shock is a leading cause of morbidity and mortality in critically ill patients worldwide.

A potential benefit of vitamin C with thiamine and low-dose hydrocortisone in the treatment of septic shock has recently been described(PMID 27940189) . The patients with septic shock who received this combination of medications weaned off pressors earlier, suffered less organ failure, and had improved mortality. The doses of vitamin C used in this trial are high, yet seemed to be safe and can be considered for use.

In this randomized controlled trial, we aim to evaluate the effect of the combination therapy (vitamin C,thiamine and hydrocortisone) on septic shock.

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225000
      • Northern Jiangsu Province People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years old or older
• Onset of septic shock within 12 hours

Exclusion Criteria:

• Systemic corticosteroid therapy within the last 3 months before septic shock
• High-dose steroid therapy
• Immunosuppression
• Pregnant
• Known glucose-6 phosphate dehydrogenase (G-6PD) deficiency
• Known hemachromatosis
• Known allergy to vitamin C, hydrocortisone, or thiamine
• Anticipated death from a preexisting disease within 90 days after randomization (as determined by the enrolling physician)
• Refusal of the attending staff or patient family

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin C,thiamine,hydrocortisone; The combination of vitamin C, thiamine, hydrocortisone : Vitamin C 2g every 6 hours x 5-days Thiamine 200mg every 12 hours x 5-days Hydrocortisone 200mg as a continuous infusion x 5-days	Drug: Vitamin C,thiamine,hydrocortisone; Vitamin C (2g) will be diluted in 100ml 0.9%NACL and administered ivd every 6 hours for 5 days or until participant is discharged from the ICU. Thiamine(200mg) will be diluted in 100ml 0.9%NACL and administered ivd every 12 hours for 5 days or until participant is discharged from the ICU. Hydrocortisone was administered 200 mg/d as a continuous infusion for 5 days or until participant is discharged from the ICU.; Other Names: Ascorbic Acid; Vitamin B1
Placebo Comparator: Placebo; Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components	Drug: Placebo; Normal saline (0.9% NaCl solution) volume to match all components; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mortality	Death from any cause at 90 days after the onset of septic shock	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality	All-cause mortality at ICU discharge	90 days after randomization
Hospital mortality	All-cause mortality at hospital discharge	90 days after randomization
28-day mortality	Death from any cause at 28 days after the onset of septic shock	28 days after randomization

Collaborators and Investigators

• Sponsor: Northern Jiangsu Province People's Hospital
• Investigators: Principal Investigator: Qingquan Lyu, Master, Northern Jiangsu Province People's Hospital

Publications and helpful links

General Publications

• Lyu QQ, Zheng RQ, Chen QH, Yu JQ, Shao J, Gu XH. Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial. Crit Care. 2022 Sep 28;26(1):295. doi: 10.1186/s13054-022-04175-x.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2019
• Primary Completion (Actual): September 20, 2021
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 9, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: septic shock; mortality; hydrocortisone; thiamine; vitamin C
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Protective Agents; Micronutrients; Antioxidants; Vitamin B Complex; Vitamins; Hydrocortisone; Ascorbic Acid; Thiamine
• Other Study ID Numbers: 2019KY-145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No