Steroids, Thiamine and Ascorbic Acid in Septic Shock

Study Overview
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Brief Summary
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The objective of this project is to determine if in patients admitted to the hospital with septic shock (population), does treatment with a bundle including hydrocortisone, thiamine, and ascorbic acid improve in-hospital or 28-day mortality (primary outcomes) or surrogate markers of illness severity including: (1) ICU or hospital length-of-stay, (2) duration of invasive mechanical ventilation, (3) duration of vasopressor administration, (4) incidence and severity of ICU delirium, and (5) illness severity (secondary outcomes).

Detailed Description
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This trial is designed as a multi-center prospective, double-blinded, randomized controlled study. The objective of this project is to determine if in patients admitted to the hospital with septic shock (population), does treatment with a bundle including hydrocortisone, thiamine, and ascorbic acid improve in-hospital or 28-day mortality (primary outcomes) or surrogate markers of illness severity including: (1) ICU or hospital length-of-stay, (2) duration of invasive mechanical ventilation, (3) duration of vasopressor administration, (4) incidence and severity of ICU delirium, and (5) illness severity (secondary outcomes). The calculated sample size is 80. Subjects will be followed for 28 days or until hospital discharge. Patients eligible for inclusion must be admitted with septic shock (as defined by SEPSIS-3) requiring vasopressors to maintain MAP ≥ 65 AND serum lactate level >2 mmol/L after adequate fluid resuscitation (generally recognized at 30 ml/kg crystalloid unless contraindicated as deemed by treating clinician) within the first three hours. The exclusion criteria are: age < 18 years, pregnant, patients with limitation of care (i.e. do not resuscitate [DNR]), known Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, and vasopressor use for > 24 hours prior to study enrollment. Patients in Arm 1 will randomized to receive usual care + hydrocortisone, thiamine and ascorbic acid. Arm 2 will be randomized to receive usual care alone. Crossover is not allowed. If a patient is randomized into study Arm 2, the treating physician may decide to administer study medications if they feel it is in the best interest of the patient. In this case the patient will continue to be analyzed in their assigned arm on an intention to treat basis. Source of participants will be in-hospital and Emergency Department patients.

Official Title
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Steroids, Thiamine and Ascorbic Acid Supplementation in Septic Shock (STASIS): A Prospective Crossover Randomized Controlled Study

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: STASIS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Septic shock admitted to the ICU within 24 hours as defined by SEPSIS-3 SEPSIS-3 defines septic shock as sepsis with the following criteria despite adequate fluid resuscitation: Vasopressor required to maintain MAP ≥ 65 AND Serum lactate level >2.0 mmol/L Age ≥ 18 years Non-pregnant Ability to consent with medical capacity or legally authorized representative (LAR) consent Exclusion Criteria: Age < 18 years Pregnant defined by negative serum HCG in all females Patients with limitation of care (i.e. DNR) Known G6PD deficiency Excluding primary admission diagnosis including the following: Acute stroke Acute coronary syndrome Active gastrointestinal bleed Burn Trauma Prisoners >1 episode of sepsis in hospital admission Vasopressor use prior to randomization for more than 24 hours

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
Interventional Model Description: A Prospective Parallel Randomized Controlled clinical Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Intervention<br>Arm will be those that are randomized to receive usual care plus hydrocortisone, thiamine and ascorbic acid. | Drug: STASIS<br>* Hydrocortisone sodium succinate, 50 mg, every 6 hours, 7 days or until ICU discharge Thiamine, 200 mg, every 12 hours, 4 days or until ICU discharge Ascorbic acid, 1,500 mg, every 6 hours, 4 days or until ICU discharge<br>|
| No Intervention: Arm 2: Usual care<br>Arm will be those that are randomized to receive usual care alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital or 28-day mortality rate | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care versus standard care in septic shock confers an in-hospital and 28-day mortality benefit | 28 days or discharge (whichever comes first) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Illness Severity (Change in SOFA Score) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers more rapid improvements in illness severity | 72 hours | 
| Hospital length-of-stay ICU LOS Duration of intubation | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved hospital length-of-stay metrics | 1 year or discharge (whichever comes first) | 
| ICU length-of-stay | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved ICU length-of-stay metrics | 90 days or discharge (whichever comes first) | 
| Vasopressor duration (days) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improvement in vasopressor requirements | 28 days or discharge (whichever comes first) | 
| ICU delerium (CAM-ICU score) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence or severity of ICU delerium | 28 days or discharge (whichever comes first) | 
| Mechanical ventilation | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence or duration of invasive mechanical ventilation. | 28 days or discharge (whichever comes first) | 
| Cardiac arrest | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence of cardiac arrest or need for cardiopulmonary resuscitation | 28 days or discharge (whichever comes first) | 
| Renal replacement therapy | o determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence of cardiac arrest or need for renal replacement therapy. | 28 days or discharge (whichever comes first) | 
| C-reactive protein | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the biochemical profiling in septic patients including a more rapid improvement in C-reactive protein | 28 days or discharge (whichever comes first) | 
| Procalcitonin | o determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the biochemical profiling in septic patients including a more rapid improvement in procalcitonin. | 28 days or discharge (whichever comes first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steroids, Thiamine, Ascorbic Acid Supplementation, Septic Shock, STASIS