Clinical trial NCT04134403: Steroids, Thiamine and Ascorbic Acid in Septic Shock
Official title: Steroids, Thiamine and Ascorbic Acid Supplementation in Septic Shock (STASIS): A Prospective Crossover Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Septic Shock
Keywords: Steroids
Thiamine
Ascorbic Acid Supplementation
Septic Shock
STASIS
Lead sponsor: Baqiyatallah Medical Sciences University
Sponsor class: OTHER
Collaborators: name: Hamadan University of Medical Science
name: Tehran University of Medical Sciences
First posted: 2019-10-22
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Prospective Parallel Randomized Controlled clinical Study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: In-hospital or 28-day mortality rate
timeFrame: 28 days or discharge (whichever comes first)
Secondary outcomes:
measure: Illness Severity (Change in SOFA Score)
timeFrame: 72 hours
measure: Hospital length-of-stay ICU LOS Duration of intubation
timeFrame: 1 year or discharge (whichever comes first)
measure: ICU length-of-stay
timeFrame: 90 days or discharge (whichever comes first)
measure: Vasopressor duration (days)
timeFrame: 28 days or discharge (whichever comes first)
measure: ICU delerium (CAM-ICU score)
timeFrame: 28 days or discharge (whichever comes first)
measure: Mechanical ventilation
timeFrame: 28 days or discharge (whichever comes first)
measure: Cardiac arrest
timeFrame: 28 days or discharge (whichever comes first)
measure: Renal replacement therapy
timeFrame: 28 days or discharge (whichever comes first)
measure: C-reactive protein
timeFrame: 28 days or discharge (whichever comes first)
measure: Procalcitonin
timeFrame: 28 days or discharge (whichever comes first)
Other outcomes:
Locations:
Study officials:
affiliation: Baqiyatallah University of Medical Scienecs
name: Amir Vahedian-Azimi, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: East Carolina University
name: Andrew C Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: