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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
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
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
Time frame: 28 days or discharge (whichever comes first)
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 28 days or discharge (whichever comes first)
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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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 28 days or discharge (whichever comes first)