Steroids, Thiamine and Ascorbic Acid in Septic Shock (STASIS)

Steroids, Thiamine and Ascorbic Acid Supplementation in Septic Shock (STASIS): A Prospective Crossover 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).

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Drug: STASIS

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1: Intervention; Arm will be those that are randomized to receive usual care plus hydrocortisone, thiamine and ascorbic acid.	Drug: STASIS; 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
NO_INTERVENTION: Arm 2: Usual care; Arm will be those that are randomized to receive usual care alone.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Baqiyatallah Medical Sciences University
• Collaborators: Tehran University of Medical Sciences; Hamadan University of Medical Science
• Investigators: Principal Investigator: Amir Vahedian-Azimi, PhD, Baqiyatallah University of Medical Scienecs; Principal Investigator: Andrew C Miller, MD, East Carolina University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2019
• Primary Completion (ANTICIPATED): November 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: October 19, 2019
• First Posted (ACTUAL): October 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 19, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Septic Shock; Steroids; Thiamine; Ascorbic Acid Supplementation; STASIS
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: STASIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No