Septic Shock
Conditions
Keywords
Steroids, Thiamine, Ascorbic Acid Supplementation, Septic Shock, STASIS
Brief summary
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
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.
Interventions
DRUGSTASIS
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
Sponsors
Hamadan University of Medical Science
Tehran University of Medical Sciences
Baqiyatallah Medical Sciences University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A Prospective Parallel Randomized Controlled clinical Study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital or 28-day mortality rate | 28 days or discharge (whichever comes first) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital length-of-stay ICU LOS Duration of intubation | 1 year or discharge (whichever comes first) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved hospital length-of-stay metrics |
| ICU length-of-stay | 90 days or discharge (whichever comes first) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved ICU length-of-stay metrics |
| Vasopressor duration (days) | 28 days or discharge (whichever comes first) | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improvement in vasopressor requirements |
| ICU delerium (CAM-ICU score) | 28 days or discharge (whichever comes first) | 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 |
| Illness Severity (Change in SOFA Score) | 72 hours | To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers more rapid improvements in illness severity |
| Cardiac arrest | 28 days or discharge (whichever comes first) | 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 |
| Renal replacement therapy | 28 days or discharge (whichever comes first) | 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. |
| C-reactive protein | 28 days or discharge (whichever comes first) | 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 |
| Procalcitonin | 28 days or discharge (whichever comes first) | 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. |
| Mechanical ventilation | 28 days or discharge (whichever comes first) | 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. |
Contacts
Primary ContactAmir Vahedian-Azimi, PhD
Backup ContactAndrew C Miller, MD
Outcome results
None listed