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Steroids, Thiamine and Ascorbic Acid in Septic Shock

Phase 3
Conditions
Septic Shock
Interventions
Drug: STASIS
Registration Number
NCT04134403
Lead Sponsor
Baqiyatallah Medical Sciences University
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1: InterventionSTASISArm will be those that are randomized to receive usual care plus hydrocortisone, thiamine and ascorbic acid.
Primary Outcome Measures
NameTimeMethod
In-hospital or 28-day mortality rate28 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 Outcome Measures
NameTimeMethod
ICU length-of-stay90 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

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

Hospital length-of-stay ICU LOS Duration of intubation1 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

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

Mechanical ventilation28 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.

Cardiac arrest28 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

Procalcitonin28 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.

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

C-reactive protein28 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

Renal replacement therapy28 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.

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