A Randomized, Double Blind, Placebo-Controlled Study to Investigate the Effects of Vitamin C, Hydrocortisone and Thiamine on the Outcome of Patients With Severe Sepsis and Septic Shock
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Hospital mortality
Study Overview
Brief Summary
The global burden of sepsis is substantial with an estimated 15 to 19 million cases per year; the vast majority of these cases occur in low income countries. New therapeutic approaches to sepsis are desperately required; considering the global burden of sepsis these interventions should be effective, cheap, safe and readily available. The aim is to study the synergistic effect of vitamin C, hydrocortisone and thiamine on survival in patients with severe sepsis and septic shock.
Detailed Description
AIM OF THE STUDY:
The goal is to determine the effects on clinical course and outcome of patients with severe sepsis and septic shock treated with vitamin C, hydrocortisone and thiamine.
BACKGROUND:
This study will be conducted in the intensive care unit of Department of Gastroenterology, University Medical Center (UMC) Ljubljana. All of the patients with severe sepsis and septic shock admitted to the Intensive Care Unit (ICU) in the past 12 hours will be screened for possible inclusion in the study. The diagnosis of severe sepsis and septic shock will be based on the 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions.
PLAN OF THE STUDY:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of severe sepsis or septic shock within 12 hours of admission in our Intensive Care Unit (ICU).
- •Informed consent.
Exclusion Criteria
- •Age < 18 years
- •Pregnancy
- •Do Not Resuscitate (DNR/DNI) with limitations of care
- •Patients with fatal underlying disease who are unlikely to survive to hospital discharge (e.g.: disseminated malignant disease)
- •Patients primarily admitted for acute coronary syndromes, acute cerebrovascular incidents or active gastrointestinal (GI) bleeds
- •Patients that need immediate surgical treatment
- •Patients with HIV and a cell count of cluster of differentiation 4 (CD4) cells < 50 mm2,
- •Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency.
- •Patients with severe sepsis/septic shock transferred from another hospital
- •Patients with features of sepsis/septic shock > 24 hours
- •Patients who require treatment with corticosteroids for an indication other than sepsis (chronic corticosteroid use, known Addison's Disease, Ulcerative colitis, Crohn's disease...)
Arms & Interventions
Active substances
Vitamin C: Vitamin C will be mixed as 1500 mg vitamin C in 50ml container, which will then be infused over 30 minutes to 1 hour. The bag will be labeled by the pharmacy as Vitamin C. The dosing schedule is 1500mg every 6 hours for 4 days or until discharge from the ICU.
Hydrocortisone: Hydrocortisone will be mixed as 50 mg of Hydrocortisone in 50 ml of 0.9 % Sodium Chloride. Patients will be treated with hydrocortisone 50mg IV q 6 hourly for 4 days or until ICU discharge.
Thiamine: Intravenous thiamine will be given in a dose of 200mg q 12 hourly for 4 days or until ICU discharge.
Intervention: Vitamin C (Drug)
Active substances
Vitamin C: Vitamin C will be mixed as 1500 mg vitamin C in 50ml container, which will then be infused over 30 minutes to 1 hour. The bag will be labeled by the pharmacy as Vitamin C. The dosing schedule is 1500mg every 6 hours for 4 days or until discharge from the ICU.
Hydrocortisone: Hydrocortisone will be mixed as 50 mg of Hydrocortisone in 50 ml of 0.9 % Sodium Chloride. Patients will be treated with hydrocortisone 50mg IV q 6 hourly for 4 days or until ICU discharge.
Thiamine: Intravenous thiamine will be given in a dose of 200mg q 12 hourly for 4 days or until ICU discharge.
Intervention: Hydrocortisone (Drug)
Active substances
Vitamin C: Vitamin C will be mixed as 1500 mg vitamin C in 50ml container, which will then be infused over 30 minutes to 1 hour. The bag will be labeled by the pharmacy as Vitamin C. The dosing schedule is 1500mg every 6 hours for 4 days or until discharge from the ICU.
Hydrocortisone: Hydrocortisone will be mixed as 50 mg of Hydrocortisone in 50 ml of 0.9 % Sodium Chloride. Patients will be treated with hydrocortisone 50mg IV q 6 hourly for 4 days or until ICU discharge.
Thiamine: Intravenous thiamine will be given in a dose of 200mg q 12 hourly for 4 days or until ICU discharge.
Intervention: Thiamine (Drug)
Control
Vitamin C placebo will consist of an identical container of 50cc normal saline (0.9% Sodium Chloride Injection) (but with no vitamin C) and will be labelled vitamin C. Placebo will be infused over 30-60 minutes as per the infusion instructions of the active vitamin. Hydrocortisone placebo will be provided in an identical 50 ml bag of 0.9% Sodium Chloride Injection. Placebo patients will receive a matching vial of 0.9% Sodium Chloride Injection.
Intervention: 0.9% Sodium Chloride Injection (Drug)
Outcomes
Primary Outcomes
Hospital mortality
Time Frame: From date of randomization till time of discharge, assessed up to 12 months
We will compare mortality between the treatment and placebo groups during the hospitalization
Secondary Outcomes
- PCT clearance(The first 4 days in Intensive Care Unit)
- 60 day mortality(60 days from inclusion in the study)
- Delta SOFA score(The first 4 days in Intensive Care Unit)
- Hospital Length of Stay(Hospital Length of Stay through the study completion, assessed up to 12 months)
- 28 day mortality(28 days from inclusion in the study)
- ICU length of stay (LOS) and ICU free days.(ICU free days is calculated as the number of days alive and out of the ICU to day 28)
- Time to vasopressor independence(Defined as the time from starting the active treatment/placebo to discontinuation of all pressors, till discharged from ICU, assessed in the first month)
Investigators
Sebastian Stefanovic, MD
Doctor of Medicine
University Medical Centre Ljubljana