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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Vitamin C,thiamine,hydrocortisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C,thiamine,hydrocortisone<br>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<br>* 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.<br>* Other names: Vitamin B1;|
| Placebo Comparator: Placebo<br>Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components | Drug: Placebo<br>* Normal saline (0.9% NaCl solution) volume to match all components<br>* Other names: Normal saline;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septic shock, vitamin C, thiamine, hydrocortisone, mortality